MEDICAL MICROBIOLOGY

LECTURE 7. VIRUSES: CLASSIFICATION, STRUCTURE AND REPLICATION. MECHANISMS OF VIRAL PATHOGENESIS.

PROPERTIES OF VIRUSES

• 1. Obligate intracellular parasites of bacteria, protozoa, fungi, algae, plants, and animals
• 2. Ultramicroscopic size, ranging from 20 nm up to 450 nm (diameter)
• 3. Not cellular in nature; structure is very compact and economical
• 4. Do not independently fulfill the characteristics of life
• 5. Inactive macromolecules outside the host cell and active only inside host cells
• 6. Basic structure consists of protein shell (capsid) surrounding nucleic acid core

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PROPERTIES OF VIRUSES

• 7. Nucleic acid of the viral genome is either DNA or RNA but not both
• 8. Nucleic acid can be double-stranded DNA, single-stranded DNA, single-stranded RNA, or double-stranded RNA
• 9. Molecules on virus surface impart high specificity for attachment to host cell
• 10. Multiply by taking control of host cell’s genetic material and regulating the synthesis and assembly of new viruses
• 11. Lack enzymes for most metabolic processes
• 12. Lack machinery for synthesizing proteins

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Size comparison of viruses with a yeast cell colored blue (eukaryotic) and various bacteria (prokaryotic).

Capside

Covering

Envelope

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Virus Nucleic Acid

particle Molecules (DNA or RNA)

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Central Core

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Matrix Proteins

Enzymes (not found in all V.)

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General Structure of Viruses

Capsids

• All viruses have capsids - protein coats that enclose and protect their nucleic acid.
• Each capsid is constructed from identical subunits called capsomers made of protein.
• The capsid together with the nucleic acid are nucleoscapsid.
• Some viruses have an external covering called envelope; those lacking an envelope are naked

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Naked Nucleocapsid Virus

Enveloped Virus

General Structure of Viruses

Two structural types:

• helical - continuous helix of capsomers forming a cylindrical nucleocapsid
• icosahedral - 20-sided with 12 corners
• vary in the number of capsomers
• Each capsomer may be made of 1 or several proteins.
• Some are enveloped.

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Assembly of helical nucleocapsids. (a) Capsomers assemble into hollow discs. (b) The nucleic acid is inserted into the center of the disc. (c) Elongation of the nucleocapsid progresses from both ends, as the nucleic acid is wound “within” the lengthening helix.

General Structure of Viruses

• Viral envelope
• mostly animal viruses
• acquired when the virus leaves the host cell
• exposed proteins on the outside of the envelope, called spikes, essential for attachment of the virus to the host cell

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Functions of Capsid/Envelope

Protects the nucleic acid when the virion is outside the host cell

Helps to bind the virion to a cell surface and assists the penetration of the viral DNA or RNA into a suitable host cell

General Structure of Viruses

• Complex viruses: atypical viruses
• Poxviruses lack a typical capsid and are covered by a dense layer of lipoproteins.
• Some bacteriophages have a polyhedral nucleocapsid along with a helical tail and attachment fibers.

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Nucleic acids

• Viral genome – either DNA or RNA but never both
• Carries genes necessary to invade host cell and redirect cell’s activity to make new viruses
• Number of genes varies for each type of virus – few to hundreds

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Nucleic Acids

• DNA viruses
• usually double stranded (ds) but may be single stranded (ss)
• circular or linear
• RNA viruses
• usually single stranded, may be double stranded, may be segmented into separate RNA pieces
• ssRNA genomes ready for immediate translation are positive-sense RNA.
• ssRNA genomes that must be converted into proper form are negative-sense RNA.

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General Structure

• Pre-formed enzymes may be present.
• polymerases – DNA or RNA
• replicases – copy DNA
• reverse transcriptase –synthesis of DNA from RNA (AIDS virus)

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How Viruses are Classified

• Main criteria presently used are structure, chemical composition, and genetic makeup.
• No taxa above Family (no kingdom, phylum, etc.)
• Currently recognized: 3 orders, 63 families, and 263 genera of viruses
• Family name ends in -viridae, i.e.Herpesviridae
• Genus name ends in -virus, Simplexvirus
• Herpes simplex virus I (HSV-I)

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Classification

• Viruses are not classified as members of the kingdoms
• Do not obey the biological taxonomy
• Generally based on:
1. Classical - eg. animal, plant, bacterial virus

system - eg. naked or enveloped virus

• Genomic - Baltimore classification

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• Serology - classification based on Diagnostic virology

- eg. Infectious bronchitis virus (IBV) of chickens

(a coronavirus) – 3 different types present, these types have significant antigenic differences, but perhaps very little genetic or biological difference between these viruses.

Classification of Viruses

The following criteria are used to classify viruses:

1. Morphology – structure of capsid

– presence or absence of envelope

2. Size of the virion
3. Type of host/host structures the virus infected

- Bacteriophages: infect bacterial cells

- Plant viruses infect plant cells

- Animal viruses are subgrouped by the tissues they attack:

1. Dermotrophic: if they infect the skin

2. Neurotrophic: if they infect nerve tissue

4. Genome composition – DNA / RNA

– ds/ss DNA and ds/ss RNA

Classification of Viruses

1. Taxonomic groups – family, subfamily, genus and species
2. The names of virus families (family) are italicized - End in Latin suffix –viridae
3. The genera (genus) end in the suffix – virus
4. The species – English common name

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Order virales e.g Mononegavirales

Family viridae e.g. Orthomyxoviridae Herpesviridae

Subfamily virinae e.g. Alphaherpesvirinae

Genus e.g. influenzavirusA Simplexvirus

Species e.g. influenza A virus human herpesvirus1

Informally:

Type e.g. herpes simplex virus 1

Strain e.g. influenza A/PR/8/34 SC16

In biology, binomial names are used. e.g Rattus rattus, Saccharomyces cerevisiae

In virology, this does not happen:

Tobacco etch potyvirus sounds OK

Influenza A influenzavirus A does not!

Bacteriophage have their own rules

Virus taxonomy

BALTIMORE CLASSIFICATION

Baltimore Classification of viruses

• The division of the viruses into classes based on genome type and mode of replication and transcription

• Suggested by David Baltimore – Seven Baltimore classes.

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• Major groups of viruses are distinguished first by their nucleic acid content as either DNA or RNA

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• RNA and DNA viruses can be single-stranded (ssRNA, ssDNA) or double-stranded (dsRNA, ssDNA)

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7 class of Baltimore classification

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Class I

• Double-stranded (ds) DNA viruses are in class 1
• The production of mRNA and genome replication in such viruses occurs as it would from the host genome.

Class II

• Single-stranded(ss) DNA viruses.
• These viruses form a double stranded DNA intermediate during replication and this intermediate used for transcription.
• RNA polymerase requires double-stranded DNA as template.

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Positive and Negative strand RNA viruses

• The production of mRNA and genome replication is much different with RNA viruses (Class III-VI).
• mRNA is the complementary base sequence to the template strand of DNA.
• In virology, mRNA is said to be plus(+) configuration.
• While its complement is said to be the minus (-) configuration.

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How does these viruses replicate?�

• Cellular RNA polymerases do not catalyze formation of RNA from an RNA template but from DNA template.
• RNA viruses whether plus, negative or double stranded require a specific RNA-dependant RNA polymerase.

Class IV

• Positive-strand of RNA viruses
• Viral genome is of the plus configuration and hence serve directly as mRNA.
• The viruses required other protein, therefore mRNA encodes a virus specific and RNA dependent RNA polymerase.
• Once synthesized, this polymerase makes complementary minus strands of RNA and then use as template to make more plus strand.

Class III and Class V

• Class III (double-stranded RNA viruses)
• Class V(negative strand RNA virus)
• mRNA must be first synthesized, however cells does not have RNA polymerase.
• To circumvent ,these viruses contain enzyme in the virion,enters cell along with the genomic RNA.
• Therefore, in this case complementary plus strand is synthesized by RNA dependant RNA polymerase and used as mRNA.
• Plus strand used as template to make more negative-strand genome.

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Class VI

• Single-stranded RNA genome that replicates with DNA intermediate.
• This RNA virus require reverse transcriptase to copy the information found in RNA to DNA.

Class VII

• Double-stranded DNA genome that replicates with RNA intermediate.
• Required reverse transcriptase
• Mechanism producing mRNA is similar in virus Class I

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Retroviruses: are enveloped viruses that have two complete copies of (+) sense RNA. They also contain the enzyme reverse transcriptase, which uses the viral RNA to form a complementary strand of DNA, which is then replicated to form a dsDNA

retro, latin for “backward”

(Class IV) in Baltimore Classification

Ambisense genome

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• A virus genome composed of ssDNA or ssRNA that is partly (+) sense and partly (-) sense.
• Example:

- Bunyaviridae ((-) sense RNA) and Arenavirus ((-) sense RNA)

Baltimore Classification - Advantages

1. Can classify between the (+) strand RNA viruses that do (Class VI) and do not (Class IV) undergo reverse transcription

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• Can classify between the dsDNA viruses that do (Class VII) and do not (Class I) carry out reverse transcription

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General Properties of RNA Viruses

• Many ssRNA viruses contain positive (+) sense RNA, and during an infection acts like mRNA and can be translated by host’s ribosomes.

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• Other ssRNA viruses have negative (-) sense RNA and the RNA acts as a template during transcription to make a complementary (+) sense mRNA.

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• Negative (-) sense RNA must carry a RNA polymerase within the virion.

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• RNA viruses must either carry enzymes or have genes for those enzymes in order to copy RNA genomes after infecting a host cell

RNA dependent RNA polymerase – Class III, IV and V

RNA VIRUSES

From Principles of Virology Flint et al., ASM Press

RNA viruses (+ve sense)

• Picornaviridae
• Togaviridae
• Flaviviridae
• Retroviridae

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MIC208 - VIROLOGY

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RNA viruses (-ve sense)

• Paramyxoviridae
• Rhabdoviridae
• Orthomyxoviridae
• Filoviridae
• Bunyaviridae
• Reoviridae (double-stranded)

MIC208 - VIROLOGY

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From Principles of Virology Flint et al., ASM Press

DNA VIRUSES