What are viruses? Classification, Structure, History, Origin, Replication, Size, Properties, Shape

What are viruses

Viruses are simple and acellular infectious agents. The branch of science which deals with the study of viruses is called virology and constitutes a significant part of microbiology. Many of human, animal and plant diseases are caused by these tiny particles. Even the recently appeared AIDS is also caused by virus. The new field of genetic engineering is also based in large part upon discoveries in virology. The word is from the Latin neuter virus referring to poison and other noxious liquids, from the same Indo-European base as Sanskrit visa poison. A virus is a small infectious agent that replicates and show living properties only inside the living cells of other organisms. They can infect all types of life forms, from multicellular organisms to unicellular organisms.

Viruses

In 1892 Dmitri Ivanovsky wrote an article describing a non-bacterial pathogen infecting tobacco plant. Martinus Beijerinck in 1898 discovered tobacco mosaic virus. Viruses are found in almost every ecosystem on Earth and are the most abundant type of biological entity. The study of viruses is known as virology. When viruses are not inside an infected cell or in the process of infecting a cell, it exists in the form of independent particles.

These viral particles, also known as virions, consist of two or three parts:

1. the genetic material made from either DNA or RNA; long molecular structure that carry genetic information.
2. a protein coat, called the capsid, which surrounds and protects the genetic material; and in some cases
3. an envelope of lipids that surrounds the protein coat. The shapes of these virus particles range from simple helical and icosahedral forms for some virus species to more complex structures for others. Most virus species have virions that are too small to be seen with an optical microscope. The average virion is about one-hundredth the size of the average bacterium.

The origins of viruses in the evolutionary history of life are unclear: some may have evolved from plasmids (pieces of DNA that can move between cells) while others may have evolved from bacteria. In evolution, viruses are an important means of horizontal gene transfer, which increases genetic diversity. Viruses are considered by some virologists to be a life form, because they carry genetic material, reproduce, and evolve through natural selection, but lack key characteristics (such as cell structure) that are generally considered necessary to count as life. Because they possess some but not all such qualities, viruses have been described as "organisms at the edge of life" and as replicators.

Viruses spread in many ways viruses in plants are often transmitted from plant to plant by insects that feed on plant sap, such as aphids; viruses in animals can be carried by blood-sucking insects. These disease-bearing organisms are known as vectors.

Influenza viruses are spread by coughing and sneezing. Norovirus and rotavirus, common causes of viral gastroenteritis, are transmitted by the faecal-oral route and are passed from person to person by contact, entering the body in food or water. HIV is one of several viruses transmitted through sexual contact and by exposure to infected blood. The range of host cells that a virus can infect is called its "host range". This can be narrow, meaning a virus is capable of infecting few species, or broad, meaning it is capable of infecting many.

History of Virus

The first images of viruses were obtained upon the invention of electron microscopy in 1931 by the German engineers Ernst Ruska and Max Knoll. In 1935 American biochemist and virologist Wendell Meredith Stanley examined the tobacco mosaic virus and found it was mostly made of protein. The tobacco mosaic virus was the first to be crystallized and its structure could therefore be elucidated in detail. The first X-ray diffraction pictures of the crystallized virus were obtained by Bernal and Fan kuchen in 1941.

Louis Pasteur was unable to find a causative agent for rabies and speculated about a pathogen too small to be detected using a microscope. In 1884, the French microbiologist Charles Chamberland invented a filter (known today as the Chamberland filter or the Pasteur Chamberland filter) with pores smaller than bacteria. Thus, he could pass a solution containing bacteria through the filter and completely remove them. In 1892, the Russian biologist Dmitri Ivanovsky used this filter to study what is now known as the tobacco mosaic virus. His experiments showed that crushed leaf extracts from infected tobacco plants remain infectious after filtration.

Ivanov sky suggested the infection might be caused by a toxin produced by bacteria, but did not pursue the idea. At the time it was thought that all infectious agents could be retained by filters and grown on a nutrient medium – this was part of the germ theory of disease. In 1898, the Dutch microbiologist Martinus Beijerinck repeated the experiments and became convinced that the filtered solution contained a new form of infectious agent.

He observed that the agent multiplied only in cells that were dividing, but as his experiments did not show that it was made of particles, he called it a contagium vivum fluidum (soluble living germ) and re-introduced the word virus. In the early 20th century, the English bacteriologist Frederick Twort discovered a group of viruses that infect bacteria, now called bacteriophages (or commonly phages), and the French-Canadian microbiologist Félix d'Herelle described viruses that, when added to bacteria on an agar plate, would produce areas of dead bacteria. By the end of the 19th century, viruses were defined in terms of their infectivity, their ability to be filtered, and their requirement for living hosts. Viruses had been grown only in plants and animals.

The second half of the 20th century was the golden age of virus discovery and most of the over 2,000 recognized species of animal, plant, and bacterial viruses were discovered during these years. In 1957 the cause of Bovine virus diarrhoea (a pesti virus) were discovered. In 1963, the hepatitis B virus was discovered by Baruch Blumberg and in 1965 Howard Temin described the first retrovirus. Reverse transcriptase, the enzyme that retroviruses use to make DNA copies of their RNA, was first described in 1970, independently by Howard Martin Temin and David Baltimore. In 1983 Luc Montagnier's team at the Pasteur Institute in France, first isolated the retrovirus now called HIV. In 1989 Michael Houghton's team at Chiron Corporation discovered Hepatitis C.

Origin of Virus

Viruses are found wherever there is life and have probably existed since living cells first evolved. The origin of viruses is unclear because they do not form fossils, so molecular techniques have been used to compare the DNA or RNA of viruses and are a useful means of investigating how they arose. In addition, viral genetic material may occasionally integrate into the germ line of the host organisms, by which they can be passed on vertically to the offspring of the host for many generations. There are three main hypotheses that aim to explain the origins of viruses.

I- Regressive Hypothesis: Viruses may have once been small cells that parasitized larger cells. Over time, genes not required by their parasitism were lost. The bacteria Rickettsia and Chlamydiae are living cells that, like viruses, can reproduce only inside host cells. They lend support to this hypothesis, as their dependence on parasitism is likely to have caused the loss of genes that enabled them to survive outside a cell. This is also called the degeneracy hypothesis or reduction hypothesis.

II- Escaped gene Theory: Some viruses may have evolved from bits of DNA or RNA that "escaped" from the genes of a larger organism. The escaped DNA could have come from plasmids (pieces of naked DNA that can move between cells) or transposons (molecules of DNA that replicate and move around to different positions within the genes of the cell). Once called "jumping genes", transposons are examples of mobile genetic elements and could be the origin of some viruses. They were discovered in maize by Barbara McClintock in 1950.] This is sometimes called the vagrancy hypothesis or the escape hypothesis. Evidence accumulated so far strongly supports the proposed that viruses originated from ‘escaped’ nucleic acid.

III- Co-evolution Hypothesis: This is also called the virus-first hypothesis and proposes that viruses may have evolved from complex molecules of protein and nucleic acid at the same time as cells first appeared on Earth and would have been dependent on cellular life for billions of years. Viroids are molecules of RNA that are not classified as viruses because they lack a protein coat. They have characteristics that are common to several viruses and are often called sub viral agents. Viroids are important pathogens of plants. They do not code for proteins but interact with the host cell and use the host machinery for their replication. Viruses are now recognized as ancient and as having origins that pre-date the divergence of life into the three domains. This discovery has led modern virologists to reconsider and re-evaluate these three classical hypotheses. The evidence for an ancestral world of RNA cells and computer analysis of viral and host DNA sequences are giving a better understanding of the evolutionary relationships between different viruses and may help to identify the ancestors of modern viruses. To date, such analyses have not proved which of these hypotheses is correct. It seems unlikely that all currently known viruses have a common ancestor, and viruses have probably arisen numerous times in the past by one or more mechanisms. Prions are infectious protein molecules that do not contain DNA or RNA. They can cause infections such as Scrapie in sheep, bovine spongiform encephalopathy ("mad cow" disease) in cattle. Although prions are fundamentally different from viruses and viroids, their discovery gives credence to the theory that viruses could have evolved from self-replicating molecules.

Structure of Virus

Viruses are sub-microscopic acellular, meaning they are biological entities that do not have a cellular structure. Therefore, they lack most of the components of cells, such as organelles, ribosomes, and the plasma membrane. A simple virus particle often designated as virion. A virion consists of a nucleic acid core, an outer protein coating or capsid, and sometimes an outer envelope made of protein and phospholipid membranes derived from the host cell. The capsid is made up of protein subunits called capsomeres. Viruses may also contain additional proteins, such as enzymes.

General Morphology of Viruses: Viruses may be classified into various morphological types on the basis of their capsid architecture. The structure of capsid and individual capsomere can be studied by electron microscopy and x-ray crystallography. Following is some of the common morphological forms of viruses (Fig. 7.1).

• Helical – These viruses are composed of a single type of capsomere stacked around a central axis to form a helical structure, which may have a central cavity, or hollow tube.
• Icosahedral – Most animal viruses are icosahedral or near-spherical with icosahedral symmetry.
• Prolate – This is an isosahedron elongated along one axis and is a common arrangement of the heads of bacteriophages.
• Enveloped viruses – Some species of virus envelope themselves in a modified form of one of the cell membranes, either the outer membrane surrounding an infected host cell or internal membranes such as nuclear membrane or endoplasmic reticulum, thus gaining an outer lipid bilayer known as a viral envelope.
• Complex viruses– These viruses possess a capsid that is neither purely helical nor purely icosahedral, and that may possess extra structures such as protein tails or a complex outer wall.

Fig. 7.1 (A-D): Morphology of viruses, A. Helical virus; B. Polyhedral virus; C. Enveloped virus; D. Complex virus

Size of Virus

Viruses display a wide diversity of sizes. In general, viruses are much smaller than bacteria. Most viruses that have been studied have a diameter between 20 and 350 nanometers. Some filoviruses have a total length of up to 1400 nm; their diameters are only about 80 nm. Most viruses cannot be seen with an optical microscope so scanning and transmission electron microscopes are used to visualize virions. The largest are the orthopoxviruses, measuring about 240 nm x 350 nm. The complex bacteriophages are about 65 nm x 200nm. Among the smallest viruses known are the enteroviruses, which are less than 30 nm. in diameter (Fig. 7.2).

Fig. 7.2: Variation of size in viruses

Shape of Virus

Viruses core in many shapes and sizes, but these are consistent and distinct for each viral family. In general, the shapes of viruses are classified into four groups: filamentous, isometric (or icosahedral), enveloped, and head and tail. Filamentous viruses are long and cylindrical. Many plant viruses are filamentous, including TMV (tobacco mosaic virus). Isometric viruses have shapes that are roughly spherical, such as poliovirus or herpesviruses. Enveloped viruses have membranes surrounding capsids. Animal viruses, such as HIV, are frequently enveloped. Head and tail viruses infect bacteria. They have a head that is similar to icosahedral viruses and a tail shape like filamentous viruses.

Viruses can be either complex (Fig. 7.3) in shape or relatively simple. Overall, the shape of the virion and the presence or absence of an envelope tell us little about what disease the virus may cause or what species it might infect, but they are still useful means to begin viral classification (Fig. 7.4).

Fig. 7.3: Diagrammatic representation of relatively complex viruses

The bacteriophage T4, with its DNA-containing head group and tail fibers that attach to host cells; adenovirus, which uses spikes from its capsid to bind to host cells; and HIV, which uses glycoproteins embedded in its envelope to bind to host cells.

Fig. 7.4 (A-D): Different shapes and size of viruses

Enveloped virions like HIV consist of nucleic acid and capsid proteins surrounded by a phospholipid bilayer envelope and its associated proteins. Glycoproteins embedded in the viral envelope are used to attach to host cells. Other envelope proteins include the matrix proteins that stabilize the envelope and often play a role in the assembly of progeny virions. Chicken pox, influenza, and mumps are examples of diseases caused by viruses with envelopes. Because of the fragility of the envelope, non-enveloped viruses are more resistant to changes in temperature, pH, and some disinfectants than are enveloped viruses.

The Protein Coat

A complete virus particle, known as a virion, consists of nucleic acid surrounded by a protective coat of protein called a capsid. These are formed from identical protein subunits called capsomeres. Viruses can have a lipid "envelope" derived from the host cell membrane. The capsid is made from proteins encoded by the viral genome and its shape serves as the basis for morphological distinction.

Virally coded protein subunits will self-assemble to form a capsid, in general requiring the presence of the virus genome. Complex viruses code for proteins that assist in the construction of their capsid.

Proteins associated with nucleic acid are known as nucleoproteins, and the association of viral capsid proteins with viral nucleic acid is called a nucleocapsid. The capsomeres forming the capsid of a virion are of two types – Pentamer, made up of five identical monomers and Hexamer, having six monomers. Each monomer is connected with the neighbouring monomers on either side with the help of bonds. Likewise, the capsomeres are also connected with each other, but the bonds between the capsomeres are weak (Fig. 7.4).

In some complex forms (e.g., influenza and herpes virus) the capsid is covered by an envelope. Some animal viruses, which are released from the host cell by an extrusion process, get coated by the host cell’s plasma membrane. This membrane eventually becomes the viral envelope. Envelope of many viruses has projections called spikes. Viruses attach themselves to the host cells by means of spikes.

Viruses, whose capsids are not covered by an envelope, are known as naked or non-enveloped viruses (e.g., TMV). In such forms the capsid facilitates the attachment of the viruses to the host surface and also protects the virus nucleic acid from the nuclease enzymes present in the biological fluids.

Nucleic Acid

Viruses differ fundamentally from cellular organisms in that they contain only one type of nucleic acid which may be either DNA or RNA. The viruses containing DNA are called Deoxy viruses, whereas those having RNA are known as Riboviruses. In general (i) all plant viruses have single stranded RNA, (ii) animal viruses have either single or (rarely) double stranded RNA or double-stranded DNA. (iii) bacterial viruses contain mostly doubles stranded DNA but can also have single stranded DNA or RNA (iv) most of the insect viruses contain RNA and only a few have DNA. DNA of some bacterial and animal viruses is circular but in others it is like RNA. The extraction of nucleic acids from viruses has shown that a virion contains only a single molecule of nucleic acid. The number of nucleotide pair in a molecule varies from 1,000-2,50,000 pairs. But the number of pairs in a specific virion is always constant. 

The amount of nucleic acid depends on the size of virion, usually larger the size of virion greater is the amount of nucleic acid (Table 7.1).

Types of Nucleic Acid

Unlike nearly all living organisms that use DNA as their genetic material, viruses may use either DNA or RNA. The virus core contains the genome or total genetic content of the virus. Viral genomes tend to be small, containing only those genes that encode proteins that the virus cannot obtain from the host cell. This genetic material may be single or double-stranded. It may also be linear or circular. While most viruses contain a single nucleic acid, others have genomes that have several, called segments.

In DNA viruses, the viral DNA directs the host cell’s replication proteins to synthesize new copies of the viral genome and to transcribe and translate that genome into viral proteins. DNA viruses cause human diseases, such as chickenpox, hepatitis B, and some venereal diseases, like herpes and genital warts.

RNA viruses contain only RNA as their genetic material. To replicate their genomes in the host cell, the RNA viruses encode enzymes that can replicate RNA into DNA, which cannot be done by the host cell. These RNA polymerase enzymes are more likely to make copying errors than DNA polymerases and, therefore, often make mistakes during transcription. For this reason, mutations in RNA viruses occur more frequently than in DNA viruses. This causes them to change and adapt more rapidly to their host. Human diseases caused by RNA viruses include hepatitis C, measles, and rabies.

Properties of Viruses

Viruses are a biological enigma. We are not sure as to their true status as a biological entity. Are they living or non-living? They exhibit characters of in animates (non-living); on the other hand, they show some properties of living as well. The picture, naturally, is quite confusing. If we accept Oparin’s hypothesis of origin of life that the inanimate and the animate worlds are merely the parts of the same evolving system, all the controversy would just vanish into air. Therefore, it may be asserted that even if the issue remains unsolved, viruses definitely have a very important place in the biological system of this universe. These could be regarded as the something unique, representing may be, a line of development which did not flourish.

Viruses are unique group of infectious agents that can be differentiated from other pathogens (both prokaryotic and eukaryotic) by the following properties:

1. The viruses are ultramicroscopic particles i.e., they are beyond the resolution of the optical microscope. The size of virus particles ranges from 18 nm to 450 nm.

2. They are not made up of cells. Their structure is very compact and economical.

3. They behave like chemicals and can be crystallized. 

4. They do not independently fulfill the characteristics of life.

5. They are inert macromolecules outside the host cell and active only inside the host cells.

6. They are geometrical in shape and form crystal like masses.

7. Their basic structure consists of a protein capsid and nucleic acid. The ‘viroids’ consist of a single strand of naked nucleic acid without protein coat.

8. Capsid is made up of repeating subunits. It encloses and protects nucleic acid. Additional layers may be very complex and contain carbohydrates, lipids and additional proteins.

9. Nucleic acid may be either DNA or RNA but not both.

10. Nucleic acid may be double stranded DNA or single stranded DNA or single stranded RNA or Double stranded RNA (Fig.7.5).

11. Molecules present on virus surface provide high specificity for host cell.

12. Viruses multiply by assembly line method. They do not divide. The cycle of multiplication include:

• Attachment of virus to host cell.
• Penetration of genetical material.
• Production of virus components by cell.
• Assembly of new viruses, and
• Release from host cell.

13. They lack enzymes for most metabolic processes.

14. They lack machinery for the synthesis of proteins.

15. They are obligate intracellular parasites of bacteria, protozoa, fungi, algae, plants and animals.

16. Many of the viruses have a close biological relationship with an arthropod or other type of vector on which they are dependent for their transmission from one host to other.

(A) Viruses are like dead things (non-living) in the following respects: -

• They can be crystallized like a sugar molecule and thus behave as chemicals.
• Outside the host, they are inert like a chemical.
• They are auto catalytic and lack functional autonomy.
• They lack any type of membranes and cell wall.
• They can be precipitated by a number of chemicals.
• They show no sign of respiration, excretion and other metabolic activities.

(B) Viruses are living molecules because of the following properties:-

• They can grow and multiply within the specific hosts.
• They show mutations.
• They can be transmitted from the diseased host plant or animal to the healthy ones.
• They react to stimuli-heat, chemicals and radiations.
• They have genetic materials either DNA or RNA or very rarely both DNA and RNA (e.g., Rous sarcoma virus, RSV).

(C) They differ from living organisms in the following properties:-

• Unit of structure of a virus is virion which lacks protoplasm and cytoplasmic organelles (c.f., cell)
• A virion contains only one type of nucleic acid, either DNA or RNA (c.f., living organisms like bacteria, algae, protozoa, which contain both of them).
• They lack fats, polysaccharides and enzymes (c.f., organisms).
• Contrary to an organism, a virus reproduces solely from genetic material i.e., (DNA/RNA).
• They cannot undergo binary fission.
• They are inert and cannot multiply outside the host cells. They are metabolically inactive outside the host cell because they do not have enzyme systems and protein synthesis machinery.

(D) Other properties:-

• They are smallest biological atoms.
• They do not have sex organs.
• They cannot move on their own.
• They do not have system for the production of energy with high potential.
• They are obligate parasites (i.e., only multiply in the living cells). Actually they are pathogens because they cause disease but not parasites.
• They exhibit host specificity (i.e., Physiological specialization).
• They are ultra filterable and ultra microscopic.
• They do not have any pigments.
• The two major components of the virus (a nucleic acid and protein shell) are produced and are assembled in the host cell.
• They are highly resistant to general poisons, antibiotics, drugs, high temperature, alkalies and salts.
• They are antigenic. On being introduced into the animal body they stimulate the production of specific antibodies.
• They utilize the ribosomes of the host cell for protein synthesis during their multiplication.

Classification of Viruses

Viruses do not fit into the established biological classification of cellular organisms. This is mainly due to pseudo-living nature of viruses; they are non-living particles with some chemical characteristics similar to those of life. Initially, viruses were classified into the following four groups on the basis of their host range, and clinical, epidemiological and pathological symptoms.

1. Plant viruses: These viruses infect only plants and depending upon the host they have been sub- divided into bacterial viruses algal viruses, fungal viruses, etc.
2. Invertebrate viruses: Viruses infecting invertebrates have been included in this group.
3. Vertebrate Viruses: This group includes viruses infecting vertebrate animals.
4. Dual-host viruses: This group includes those viruses which infects two different hosts mentioned above.

Holmes (1948) included all viruses in a single order Virales which were divided into three suborders.

1. Phagineae : This sub-order includes viruses infecting bacteria i.e., bacteriophage.
2. Phytophagineae : It includes viruses infecting plants.
3. Zoophagineae : It includes viruses infecting animals.

(A). Based on information obtained from ultracentrifuge and electron microscopic studies, Lwoff, Horne and Tournier (1962) proposed a comprehensive scheme for the classification of viruses which consisted of phylum-class-order-family-sub-family-genus-species-strain/type. The International Committee on the Nomenclature of Viruses accepted many principles of this system. Lwoff et al. system emphasized that the viruses should be grouped according to their shared properties rather that the properties of the cells or organisms they infect.

The four criteria on which this hierarchical system is based are:

1. Nature of the nucleic acid (RNA or DNA).
2. Symmetry or the capsid.
3. Presence or absence of an envelope.
4. Dimensions of the virion and capsid.

A brief outline of PCNV (A Provisional Committee on Nomenclature of Viruses) classification is as follows:

(PCVN Classification)

Phylum-Vira is divided into two subphyla on the basis of type of nucleic acid present.

(a) Sub-phylum: Deoxyvira- These are DNA containing viruses. This subphylum is divided into three classes on the basis of the symmetry.

(b) Sub-phylum: Ribovira- This includes RNA containing viruses. These are also further divided on the basis of symmetry as follows:

(B) David Baltimore classification

Baltimore classification is a classification system which places viruses into one of seven groups depending on a combination of their nucleic acid (DNA or RNA), strandedness (single-stranded or double-stranded), and method of replication. 

• Group I : double-stranded DNA viruses
• Group II : single-stranded DNA viruses
• Group III : double-stranded RNA viruses
• Group IV : positive-sense single-stranded RNA viruses
• Group V : negative-sense single-stranded RNA viruses
• Group VI : reverse transcribing Diploid single-stranded RNA viruses
• Group VII : reverse transcribing Circular double-stranded DNA viruses

(C) ICTV Classification

International Committee on Taxonomy of Viruses has suggested ‘family’ as the highest taxonomic category for viruses. The International Committee on Taxonomy of Viruses devised and implemented several rules on the naming and classification of viruses early in the 1990's. To this day they oversee the naming and placement of viral species into the framework.

The system shares many features with the classification system of cellular organisms, such as taxon structure. Viral classification starts at the level of order and follows as thus, with the taxon suffixes given in italics:

• Order − (virales)
• Family − (viridae)
• Subfamily − (virinae)
• Genus − (virus)
• Species − (virus)

However, this system of nomenclature differs from other taxonomic codes on several points. A minor point is that names of orders and families are italicized, as in the ICBN. Most notably, species names generally take the form of [Disease] Virus. The recognition of orders is very recent and has been deliberately slow; to date, only three have been named, and most families remain unplaced. Approximately 80 families and 4000 species of virus are known.

(D) Classification of virus on the basis of genetic material

The classification of viral on the basis of nucleic acids is given in the Fig. 7.5. According to this classification the virus can be categorized as:

DNA viruses:

• Group I: viruses possess double-stranded DNA and include such virus families as Herpesviridae (examples like HSV1 (oral herpes), HSV2 (genital herpes), VZV (chickenpox), EBV (Epstein-Barr virus), CMV (Cytomegalovirus)), Poxviridae (smallpox) and many tailed bacteriophages. The mimivirus was also placed into this group (Table 7.2).
• Group II: viruses possess single-stranded DNA and include such virus families as Parvoviridae and the important bacteriophage M13.

RNA viruses:

• Group III: viruses possess double-stranded RNA genomes, e.g., rotavirus. These genomes are always segmented.
• Group IV: viruses possess positive-sense single-stranded RNA genomes. Many well-known viruses are found in this group, including the picornaviruses (which is a family of viruses that includes well-known viruses like Hepatitis A virus, enteroviruses, rhinoviruses, poliovirus, and foot-and-mouth virus), SARS virus, hepatitis C virus, yellow fever virus, and rubella virus.
• Group V: viruses possess negative-sense single-stranded RNA genomes. The deadly Ebola and Marburg viruses are well known members of this group, along with influenza virus, measles, mumps and rabies.

Fig. 7.5: Viral classification on the basis of nucleic acids

Reverse transcribing viruses

• Group VI: viruses possess single-stranded RNA genomes and replicate using reverse transcriptase. The retroviruses are included in this group, of which HIV is a member.
• Group VII: viruses possess double-stranded DNA genomes and replicate using reverse transcriptase. The hepatitis B virus can be found in this group.

(E). The different families of RNA viruses are distinguished from one another by their nucleic acid content, their capsid shape and the presence and absence of an envelope. Some important human, animal and plant virus families are given in Table 7.3.

Table 7.2: Classification of major groups of DNA viruses that cause human, animal and plant diseases.

Table-7.3: Classification of major groups of RNA viruses that cause human, animal and plant diseases.

Based on information obtained from ultracentrifuge and electron microscopic studies Lwott, Home and Tournier (1962) proposed a system of classification of Viruses (known as LHT system) which was accepted by ICVN (International Committee for virus Nomenclature (1966).

Classification is based upon

• type of nucleic acid
• Molecular weight of virus
• Shape and size of virus
• Symmetry of virus
• Number of protein subunits in a capsid
• Diameter of nucleic acid coil
• presence of outer envelope
• Intercellular multiplication
• temperature inactivation of virus
• method of viral transmission
• symptoms of virus on the host plant.

Replication of Viruses

Viruses multiply only in living cells. The host cell must provide the energy and synthetic machinery and the low molecular-weight precursors for the synthesis of viral proteins and nucleic acids. Viral replication is the formation of biological viruses during the infection process in the target host cells. Viruses must first get into the cell before viral replication can occur. From the perspective of the virus, the purpose of viral replication is to allow production and survival of its kind. By generating abundant copies of its genome and packaging these copies into viruses, the virus is able to continue infecting new hosts. Replication between viruses is greatly varied and depends on the type of genes involved in them. Most DNA viruses assemble in the nucleus while most RNA viruses develop solely in cytoplasm. The virus replication (Fig.7.6) occurs in seven stages, namely;

1. Adsorption/ Attachment
2. Entry
3. Uncoating
4. Replication
5. Transcription / mRNA production
6. Synthesis of virus components
7. Virion assembly 
8. Release (Liberation Stage)

Fig. 7.6: Generalized replication process in viruses

1. Adsorption: The virus attaches to the cell membrane of the host cell. It then injects its DNA or RNA into the host to initiate infection. Attachment is a specific binding between viral capsid proteins and specific receptors on the host cellular surface. This specificity determines the host range of a virus. For example, HIV infects a limited range of human leucocytes. This is because its surface protein, gp120, specifically interacts with the CD4 molecule – a chemokine receptor – which is most commonly found on the surface of CD4+ T-Cells. This mechanism has evolved to Favour those viruses that infect only cells in which they are capable of replication. Attachment to the receptor can induce the viral envelope protein to undergo changes that results in the fusion of viral and cellular membranes, or changes of non-enveloped virus surface proteins that allow the virus to enter.

2. Entry: The cell membrane of the host cell invaginates the virus particle, enclosing it in a pinocytotic vacuole. This protects the cell from antibodies, as in the case of the HIV virus.

Penetration follows attachment: Virions enter the host cell through receptor�mediated endocytosis or membrane fusion. This is often called viral entry. The infection of plant and fungal cells is different from that of animal cells. Plants have a rigid cell wall made of cellulose, and fungi one of chitin, so most viruses can get inside these cells only after trauma to the cell wall. Nearly all plant viruses (such as tobacco mosaic virus) can also move directly from cell to cell, in the form of single-stranded nucleoprotein complexes, through pores called plasmodesmata. Bacteria, like plants, have strong cell walls that a virus must breach to infect the cell. Given that bacterial cell walls are much thinner than plant cell walls due to their much smaller size, some viruses have evolved mechanisms that inject their genome into the bacterial cell across the cell wall, while the viral capsid remains outside.

3. Uncoating: Uncoating is a process in which the viral capsid is removed: This may be by degradation by viral enzymes or host enzymes or by simple dissociation; the end-result is the releasing of the viral genomic nucleic acid.

4. Replication: Replication of viruses involves primarily multiplication of the genome. Replication involves synthesis of viral messenger RNA (mRNA) from "early" genes (with exceptions for positive sense RNA viruses), viral protein synthesis, possible assembly of viral proteins, then viral genome replication mediated by early or regulatory protein expression. This may be followed, for complex viruses with larger genomes, by one or more further rounds of mRNA synthesis: "late" gene expression is, in general, of structural or virion proteins (Fig. 7.7 and 7.8).

(a) Genome replication: The genetic material within virus particles, and the method by which the material is replicated, varies considerably between different types of viruses.

• (i) DNA viruses: The genome replication of most DNA viruses takes place in the cell's nucleus. If the cell has the appropriate receptor on its surface, these viruses enter the cell sometimes by direct fusion with the cell membrane (e.g., herpesviruses) or – more usually – by receptor mediated endocytosis. Most DNA viruses are entirely dependent on the host cell's DNA, RNA synthesizing machinery and RNA processing machinery. Viruses with larger genomes may encode much of this machinery themselves. In eukaryotes the viral genome must cross the cell's nuclear membrane to access this machinery, while in bacteria it need only enter the cell.
• (ii) RNA viruses: Replication usually takes place in the cytoplasm. RNA viruses can be placed into four different groups depending on their modes of replication. The polarity (whether or not it can be used directly by ribosomes to make proteins) of single-stranded RNA viruses largely determines the replicative mechanism; the other major criterion is whether the genetic material is single-stranded or double-stranded. All RNA viruses use their own RNA replicase enzymes to create copies of their genomes.
• (iii) Reverse transcribing viruses: These have ssRNA (Retroviridae, Metaviridae, Pseudoviridae) or dsDNA (Caulimoviridae, and Hepadnaviridae) in their particles. Reverse transcribing viruses with RNA genomes (retroviruses), use a DNA intermediate to replicate, whereas those with DNA genomes (pararetroviruses) use an RNA intermediate during genome replication. Both types use a reverse transcriptase, or RNA dependent DNA polymerase enzyme, to carry out the nucleic acid conversion. Retroviruses integrate the DNA produced by reverse transcription into the host genome as a provirus as a part of the replication process; pararetroviruses do not, although integrated genome copies of especially plant pararetroviruses can give rise to infectious virus. They are susceptible to antiviral drugs that inhibit the reverse transcriptase enzyme, e.g., zidovudine and lamivudine. An example of the first type is HIV, which is a retrovirus. Examples of the second type are the Hepadnaviridae, which includes Hepatitis B virus.

5. Transcription / mRNA production

For some RNA viruses, the infecting RNA produces messenger RNA (mRNA). This is translation of the genome into protein produces. For others with negative stranded RNA and DNA, viruses are produced by transcription then translation. The mRNA is used to instruct the host cell to make virus components. The virus takes advantage of the existing cell structures to replicate itself.

Fig. 7.7:A typical virus replication cycle

Fig. 7.8: Replication process in typical bacteriophage

6. Synthesis of Virus components: The following components are manufactured by the virus through the host's existing organelles:

• Viral protein synthesis: virus mRNA is translated on cell ribosomes into two types of virus protein.
• Structural: the proteins which make up the virus particle are manufactured and assembled.
• Non – structural: not found in particle, mainly enzymes for virus genome replication.
• Viral nucleic acid synthesis (genome replication) new virus genome is synthesized, templates are either the parental genome or with single stranded nucleic acid genomes, newly formed complementary strands. By a virus called polymerate or replicate in some DNA viruses by a cell enzyme. This is done in rapidly dividing cells.

7. Assembly: A virion is simply an active or intact virus particle. In this stage, newly synthesized genome (nucleic acid), and proteins are assembled to form new virus particles. This may take place in the cell's nucleus, cytoplasm, or at plasma membrane for most developed viruses. Following the structure-mediated self-assembly of the virus particles, some modification of the proteins often occurs. In viruses such as HIV, this modification (sometimes called maturation) occurs after the virus has been released from the host cell.

8. Release (Liberation Stage) – The viruses, now being mature are released by either sudden rupture of the cell, or gradual extrusion (budding) of enveloped viruses through the cell membrane. The new viruses may invade or attack other cells or remain dormant in the cell. The viruses can be released from the host cell by ‘lysis’, a process that kills the cell by bursting its membrane and cell wall if present: This is a feature of many bacterial and some animal viruses. Some viruses undergo a lysogenic cycle where the viral genome is incorporated by genetic recombination into a specific place in the host's chromosome (Fig. 7.9). The viral genome is then known as a "provirus" or, in the case of bacteriophages a "prophage". Whenever the host divides, the viral genome is also replicated. The viral genome is mostly silent within the host. At some point, the provirus or prophage may give rise to active virus, which may lyse the host cells. Enveloped viruses (e.g., HIV) typically are released from the host cell by budding. During this process the virus acquires its envelope, which is a modified piece of the host's plasma or other, internal membrane. 

In the case of bacterial viruses, the release of progeny virions takes place by lysis of the infected bacterium. However, in the case of animal viruses, release usually occurs without cell lysis.

Fig. 7.9: Lytic and lysogenic cycle in bacteriophage

Structure of Tobacco Mosaic Virus (TMV)

TMV is a simple rod-shaped helical virus consisting of centrally located single- stranded RNA (5.6%) enveloped by a protein coat (94.4%). The rod is considered to be 3,000 Å in length and about 180 Å in diameter. The protein coat is technically called ‘capsid’. R. Franklin estimated 2,130 sub-units, namely, capsomeres in a complete helical rod and 49 capsomeres on every three turns of the helix; thus there would be about 130 turns per rod of TMV.

The diameter of RNA helix is about 80 Å and the RNA molecule lies about 50 Å inward from the outer-most surface of the rod. The central core of the rod is about 40 Å in diameter. Each capsomere is a grape like structure containing about 158 amino acids and having a molecular weight of 17,000 Dalton as determined by Knight.

The ssRNA is little more in length (about 3300 Å) slightly protruding from one end of the rod. The RNA molecule consists of about 7300 nucleotides; the molecular weight of the RNA molecule being about 25,000 Dalton.

Lifecycle (Replication) of Tobacco Mosaic Virus (TMV)

Plant viruses like TMV penetrate and enter the host cells in toto and their replication completes within such infected host cells (Fig. 7.10). Inside the host cell, the protein coat dissociates, and viral nucleic acid becomes free in the cell cytoplasm.

Fig. 7.10: Tobacco Mosaic Virus (TMV)  A. Surface View, B. An enlarged view showing RNA capsomere arrangement, C. View in section

Although the sites for different steps of the viral multiplication and formation of new viruses have not yet been determined with absolute certainty, the studies suggest ha alter becoming free in the cell cytoplasm the viral-RNA moves into the nucleus (possibly into the nucleolus).The viral RNA first induces the formation of specific enzymes called ‘RNA polymerases’ the single stranded viral-RNA synthesizes an additional RNA strand called replicative RNA.

This RNA strand is complementary to the viral genome and serves as ‘template’ for producing new RNA single strand which is the copy of the parental viral-RNA. The new viral-RNAs are released from the nucleus into die cytoplasm and serve as messenger-RNAs (mRNAs). Each mRNA, in cooperation with ribosomes and t-RNA of the host cell directs the synthesis of protein subunits.

After the desired protein sub-units (capsomeres) have been produced, the new viral nucleic acid is considered to organize the protein subunit around it resulting in the formation of complete virus particle, the virion. No ‘lysis’ of the host cell, as seen in case of virulent bacteriophages, takes place. The host ells remain alive and viruses move from one cell to the other causing systemic infection. When transmitted by some means the viruses infect other healthy plants.

Summary

• A virus is a small infectious agent that replicates and show living properties only inside the living cells of other organisms. They can infect all types of life forms, from multicellular organisms to unicellular organisms.
• Viruses of all shapes and sizes consist of a nucleic acid core, an outer protein coating or capsid, and sometimes an outer envelope. Viruses are classified into four groups based on shape: filamentous, isometric (or icosahedral), enveloped, and head and tail.
• Many viruses attach to their host cells to facilitate penetration of the cell membrane, allowing their replication inside the cell.
• Non-enveloped viruses can be more resistant to changes in temperature, pH, and some disinfectants than are enveloped viruses.
• The virus core contains the small single- or double-stranded genome that encodes the proteins that the virus cannot get from the host cell.
• Viral populations do not grow through cell division, because they are acellular. Instead, they use the machinery and metabolism of a host cell to produce multiple copies of themselves, and they assemble in the cell.

Glossary

• Assembly: The gathering and replication of viruses within a cell by using the metabolism of the host organism.
• Attachment: The condition where the capsid proteins of the virus bind to certain receptors of the host organism.
• Capsid: The protein covering of a virus particle.
• Envelope: A lipid casing that surrounds the capsid that covers a virus. A viral envelope assists the virus in infiltrating the cells of the host organism.
• Gene Expression: An activity where information from a gene is made into functional gene material.
• Genome Replication: The reproduction of genetic material, particularly that in the structure of DNA.
• Latent Infection: A viral infection that exists in dormancy and does not exhibit symptoms.
• Maturation: The phase during replication at which a virus becomes infectious.
• mRNA: A form of ribonucleic acid which carries copied genetic information from DNA to the cell ribosome.
• Nucleocapsid: The composition of a virus that includes the DNA, RNA, and the capsid protein cover.
• Penetration: The process of the virus entering the cell of the host organism, causing infection.
• Receptor: A specific type of molecule found on a cell membrane that a virus is able to attach to.
• Release: The process of the death of a host cell that discharges a virus.
• Uncoating: A condition when the protein capsid of the virus is unsheathed due to enzymes of the cells of the host organism.
• Vector: Insects, such as mosquitoes or ticks, that carries disease from one organism to another.
• Virions: A virus particle, which invades the cells of a host organism, causing infection.
• Virus Attachment Protein: A specific protein found on a virus in charge of fixating to the receptor.

FAQ :

Who discovered virus?

Dmitri Ivanovsky

Who coined term virus?

microbiologist Martinus Beijerinck

What is the full form of virus?

Vital Information Resources Under Siege

Who isolated plant viruses first?

Dmitri Ivanovsky