Thursday, January 7, 2021

Virus

 Virus

Viruses are the smallest known infective agents and the simplest form of life known. They do not possess any cellular organization and they do not fall into the category of unicellular microorganisms.

Properties of Viruses

1. Viruses do not have a cellular organization.

2. They contain only one type of nucleic acid, either DNA or RNA but never both.

3. They are obligate intracellular parasites.

4. They lack the enzymes necessary for protein and nucleic acid synthesis and are dependent for replication on the synthetic machinery of host cells.

Morphology of viruses

                                                        thebiologynotes.com

Size: Viruses are much smaller than bacteria. Their small size and ‘filterability’ (ability to pass through filters that can hold back bacteria) led to their recognition as a separate class of infectious agents. They were termed as filterable agents upon discovery.

Viruses vary widely in size from 20 nm to 300 nm. The largest among them is pox virus (300 nm) and is as large as the smallest bacteria (mycoplasma).  The Smallest viruses are the parvovirus (about 20 nm).

They are too small to be seen under the light microscope. Some of the larger viruses, such as poxviruses can be seen under the light microscope when suitably stained.

Shape:

Shape of virus varies with different groups of viruses. Most of the animal viruses are roughly spherical, some are irregular and pleomorphic. Poxviruses are brick-shaped, rabies virus is bullet-shaped, tobacco mosaic virus is rod-shaped. Bacteriophages have a complex morphology.

They consist of nucleic acid core surrounded by a protein coat called capsid. The capsid is composed of a large number of capsomers which are polypeptide molecules arranged symmetrically.  The capsid with the enclosed nucleic acid is known as nucleocapsid.

Functions of Capsid

i. It protects the viral genome from physical destruction and enzymatic inactivation.

ii. It provides binding sites for the virus to attach to specific receptor sites on the host cell.

iii. It facilitates the assembly and packaging of virus after replication.

iv. It serves as a vehicle of transmission from one host to another.

v. It is antigenic and specific for each virus type and is of importance in the host’s defence to virus infection.

vii. It provides the structural symmetry to the virus particle.

Viral architecture is grouped into three based on the arrangement of morphologic subunits:

(1) Icosahedral symmetry (2) Helical symmetry (3) Complex structures.

1. Icosahedral Symmetry

An icosahedral (icosa, meaning 20 in Greek) is a polygon with 12 vertices or corners and 20 facets or sides. Each facet is in the shape of an equilateral triangle. Two types of capsomers constitute the icosahedral capsid. They are the pentagonal capsomers at the vertices (pentons) and the hexagonal capsomers making up the facets (hexons).  Example - Adenovirus

2. Helical Symmetry

The nucleic acid and the capsomers are wound together in the form of a helix or spiral. Examples: Tobacco Mosaic Virus and rabies.

3. Complex Symmetry

They do not have either icosahedral or helical symmetry due to complexity of their capsid structure.  Example is Poxviruses.  Some bacteriophage such as T4 phage have icosahedral head and helical tail and thus have complex symmetry.

Enveloped Virus : Virus may be enveloped or nonenveloped (naked). In enveloped Virus, the envelope or outer covering of virus is derived from the plasma membrane of the host cell during their replication. The envelope is lipoprotein in nature. The lipid is of host cell origin while the protein is virus encoded.

Enveloped viruses are susceptible to the action of lipid solvents such as ether, chloroform and detergents, whereas most viruses existing as naked capsids are more likely to be resistant to them.

In virus particle, the glycoproteins appear as projecting spikes on the outer surface of the envelope.  These are known as peplomers (from peplos, meaning envelope). A virus may have more than one type of peplomers, e.g., the influenza virus carries two kinds of peplomers, the hemagglutinin which is a triangular spike and the neuraminidase which is a mushroom shaped structure. Envelope confer chemical, antigenic and biological properties on viruses.

Functions of Peplomers

i. Many peplomers mediate attachment of the virus to the host-cell receptors to initiate the entrance of the virion into the cell.

ii. Some viral glycoproteins attach to receptors on red blood cells, causing these cells to agglutinate (hemagglutination).

iii. Some possess enzymatic activity like neuraminidase which cleave neuraminic acid from host cell glycoproteins.

iv. Glycoproteins are major antigens

Viral Nucleic Acids

Viruses contain a single kind of nucleic acid—either DNA or RNA—that encodes the genetic information necessary for replication of the virus. The genome may be single-stranded or double-stranded, circular or linear, and segmented or nonsegmented. The type, structure and size of nucleic acid are used for classifying viruses.


sciencedirect.com

Viral replication

The genetic information necessary for viral replication is in the viral nucleic acid but since virus lack biosynthetic enzymes they depend on the host cell for replication. The viral replication / multiplication cycle can be divided into six sequential phases

1.  Adsorption or attachment

2. Penetration

3. Uncoating

4. Biosynthesis/Replication

5. Maturation

6. Release


researchgate.net

1. Adsorption or Attachment

Virus come in contact with host cells by random collision followed by specific adsorption or attachment.  This is mediated by the binding of virion surface structures, known as ligands, to receptors on cell surface. In case of influenza virus, hemagglutinin (a surface glycoprotein) binds specifically to sialic acid residue of glycoprotein receptor sites on the surface of respiratory epithelium. In case of human immunodeficiency virus, surface glycoprotein gp 120 acts as a ligand which binds to the CD4 glycoprotein on the surface of mature T lymphocytes. Rabies virus binds to the acetylcholine receptor found on neural cells.

2. Penetration

After adsorption, the virus particle is taken up inside the cell.

Some viruses accomplish this by receptor mediated endocytosis or viropexis.  Here uptake of the ingested virus particles within endosomes occurs. Most nonenveloped viruses enter the cell by viropexis.

Enveloped viruses fuse their membranes with host cell membranes and deliver the nucleocapsid or genome directly into the host cytoplasm.

3. Uncoating

This is the stripping of virus of its capsid so that the nucleic acid is released into the cell. Uncoating is effected by the action of host cell lysosomal enzymes. Genome of most RNA viruses remain in the cytoplasm, while genome of DNA viruses, except poxviruses, are delivered to the nucleus.

4. Biosynthesis/Replication

This phase includes synthesis of the viral nucleic acid, capsid protein and enzymes necessary in the various stages of viral synthesis, assembly and release. In addition to these, some ‘regulator proteins’ are also synthesized which shut down the normal cellular metabolism and direct the production of viral components.

Most DNA viruses synthesize their nucleic acid in the host cell nucleus. The exception is the poxviruses, which synthesize the components in the host cell cytoplasm.

Most RNA viruses synthesize their components in the cytoplasm, except orthomyxoviruses, some paramyxoviruses and retroviruses which synthesise few of the components in the nucleus.

Viral proteins are synthesised in the cytoplasm.

Steps of Biosynthesis

i. Transcription of messenger RNA (mRNA) from the viral nucleic acid.

ii. Translation of the mRNA into ‘early proteins’. These are enzymes required for the synthesis of virus components and to induce shutdown of host protein and host nucleic acid synthesis.

iii. Replication of viral nucleic acid.

iv. Synthesis of ‘late’ or structural proteins, which are the components of daughter virion capsids.

5. Maturation

Assembly of the various viral components into virions occur during maturation.  This may take place either in the nucleus (herpes and adenoviruses) or cytoplasm (picorna and poxviruses).

In case of enveloped viruses, the envelopes are derived from the host cell nuclear membrane (herpes virus) or host cell plasma membrane (orthomyxoviruses and paramyxoviruses).

6. Release

Viruses are released from cells after lysis of the cell or by exocytosis or by budding from the plasma membrane.

Viruses that exist as nucleocapsids are released by the lysis of the host cell (polioviruses) or they may be extruded by a process known as reverse phagocytosis.

Release of enveloped viruses occurs as budding from the plasma membrane without killing the cell.

Eclipse phase

During viral multiplication the virus cannot be demonstrated inside the host cell from the stage of penetration till the appearance of mature virions. This period is known as the ‘eclipse phase’. The time taken for a single cycle of replication is about 15-30 minutes for bacteriophages and about 15-30 hours for animal viruses.

Abnormal replicative cycles

1. Incomplete Viruses

A proportion of daughter virions that are produced may not be infective due to defective assembly.  Such ‘incomplete viruses’ are seen in large numbers when cells are infected with a high dose of influenza virus.  The virus yield will have a high hemagglutinin titer but low infectivity. This is known as the von Magnus phenomenon.

2. Abortive Infections

Abortive infections fail to produce infectious progeny, either because the cell may be nonpermissive and unable to support the expression of all viral genes or because the infecting virus may be defective due to lack of some functional viral genes.

3. Latent Infection

During a latent infection, there will be the persistence of viral genomes and expression of none or a few viral genes, but the infected cell continue to survive.

4. Defective Viruses

Viruses which are genetically deficient and incapable of producing infectious daughter virions without the helper activity of another virus are known as’ defective viruses’. Progeny virions will be formed only if the cells are simultaneously infected with a helper virus, which is a normal virus.

Example

i. Hepatitis D virus and adeno-associated satellite viruses which replicate only in the presence of their helper viruses—hepatitis B and adenoviruses respectively.

ii. Rous sarcoma virus (RSV) cannot code for the synthesis of the viral envelope in the absence of its helper virus (avian leucosis virus).  Infectious progeny of RSV results only if the helper virus contribute to the synthesis of the envelope.


Baltimore classification of viruses based on replication mechanisms

Viruses have been categorized into six classes by Baltimore (1970) based on their replication mechanisms.

Sl. No

Class

Feature

           1

Single stranded DNA viruses

DNA molecule moves into the host cell nucleus and is converted into the duplex form. Transcription is achieved by host enzymes. Example - Parvovirus

           2

Double stranded DNA viruses

DNA enters the host cell nucleus and uses the host cell enzymes for transcription

Example -  Hepadnaviruses,  Poxviruses

              3

Single stranded RNA viruses

 

Depending on the method of mRNA transcription, these are classified into two categories

Positive strand (plus strand, positive sense): The viral RNA acts as the mRNA. Viral RNA is infectious by itself and is translated directly into viral proteins in the host cell cytoplasm.

Example -Picorna, Togaviruses.

            4

The negative strand (minus sense) RNA viruses: The RNA is ‘antisense’, with polarity opposite to mRNA. They possess their own RNA polymerases for mRNA transcription

Example – Rhabdo virus, Orthomyxo virus, Paramyxovirus

            5

Double stranded RNA viruses

The DS RNA is transcribed to mRNA by viral polymerases

Example - Reoviruses

         6

Retrovirus

SS RNA genome is converted into an RNA: DNA hybrid by the viral reverse transcriptase enzyme. Double stranded DNA is then synthesized from the RNA: DNA hybrid. The double stranded DNA form of the virus (provirus) is integrated into the host cell chromosome. This integration may lead to transformation of the cell and development of neoplasia.

 

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