VIRUS STRUCTURE AND CLASSIFICATION

Claude MUVUNYI M.D., Ph.D.

Terminology

Virion: The complete infectious virus particle.

Capsid: The protein coat that surrounds nucleic acid.

Nucleocapsid: The nucleic acid plus the capsid.

The nucleocapsid may be enclosed inside an ENVELOPE containing proteins encoded by the virus.

STRUCTURE UNITS are the smallest equivalent building units of the capsid.

Capsomeres: The structural protein units that made up the capsid.

In 1962, Caspar et al. defined the following terms:

General structure of viruses

Viruses composed of nucleic acid either DNA or RNA, surrounded by a protein coat called the capsid.

The capsid is composed of small structural units called capsomeres.

The capsid protects nucleic acid from inactivation by the outer physical conditions.

Some viruses have additional lipoprotein envelope , composed of virally coded protein and host lipid. The viral envelope is covered with glycoprotein spikes.

General structure of viruses Some viruses have enzymes inside the virion. All ss- RNA

viruses with negative polarity have the enzyme transcriptase ( RNA dependent RNA polymerase) inside virions.

Virus Shapes

Viruses may be classified into several morphological types on the basis of their capsid architecture as revealed by electron microscopy and a technique called x-ray crystallography.

General morphology

Virus structure

• Self assembly of virus capsids follows two basic patterns:– Helical symmetry, in which the protein subunits and the nucleic acid are arranged in a helix.

– Icosahedral symmetry, in which the protein subunits assemble into a symmetric shell that covers the nucleic acid-containing core.

Virus structure• Larger viruses often have a complex

architecture consisting of both helical and isometric

symmetries confined to different structural components.

• Small viruses, e.g., hepatitis B virus or the members of the picornavirus or parvovirus family, are orders of magnitude more resistant than are the larger complex viruses, e.g. members of the herpes or retrovirus families.

Basic virus structure

Capsid protein Nucleocapsid Naked

capsid virus

DNA

RNAor =+

Nucleocapsid Lipid membrane, glycoproteins Enveloped virus+

Capsid symmetryIcosahedral Helical

Naked capsid

Enveloped

Lipid

Glycoprotein

Matrix

Icosahedral naked capsid viruses

AdenovirusElectron micrograph

Foot and mouth disease virusCrystallographic model

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Helical naked capsid viruses

Tobacco mosaic virusElectron micrograph

Tobacco mosaic virusModel

RNA Protein

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Icosahedral enveloped viruses

Herpes simplex virusElectron micrograph

Herpes simplex virusNucleocapsid cryoEM model

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Helical enveloped viruses

Influneza A virusElectron micrograph

ParamyxovirusElectron micrograph

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Properties of enveloped viruses• Envelope is sensitive to

– Drying– Heat– Detergents– Acid

• Consequences– Must stay wet during transmission– Transmission in large droplets and secretions– Cannot survive in the gastrointestinal tract– Do not need to kill cells in order to spread– May require both a humoral and a cellular immune

response

Adapted from Murray, P.R. Rosenthal K.S., Pfaller, M.A. (2005) Medical Microbiology, 5th edition, Elsevier Mosby, Philadelphia, PA Box 6-5

Properties of naked capsid viruses

• Capsid is resistant to– Drying– Heat– Detergents– Acids– Proteases

• Consequences– Can survive in the gastrointestinal tract– Retain infectivity on drying– Survive well on environmental surfaces– Spread easily via fomites– Must kill host cells for release of mature virus particles– Humoral antibody response may be sufficient to neutralize infection

Adapted from Murray, P.R. Rosenthal K.S., Pfaller, M.A. (2005) Medical Microbiology, 5th edition, Elsevier Mosby, Philadelphia, PA , Box 6-4

FIVE BASIC STRUCTURAL FORMS OF VIRUSES IN NATURE

Naked icosahedral e.g. poliovirus, adenovirus, hepatitis A virus

Naked helical e.g. tobacco mosaic virus. So far no human viruses with this structure are known

Enveloped icosahedral e.g. herpes virus, yellow fever virus, rubella virus

Enveloped helical e.g. rabies virus, influenza virus, parainfluenza virus, mumps virus, measles virus

Complex e.g. poxvirus

CLASSIFICATION OF VIRUS

Naming of VirusesUsually based on data available when a virus is discovered: Diseases viruses are associated with, e.g.: Poxvirus,

Hepatitis virus, HIV, Measles virus.

Cytopathology occuring during infection, e.g.: Respiratory Syncytial virus, Cytomegalovirus.

Site of infection, e.g.: Adenovirus, Enterovirus, Rhinovirus, Enterovirus.

Places where viruses were found or people who discovered them, e.g.: Epstein-Barr virus, Rous Sarcoma, Rift Valley Fever.

Biochemical features, e.g.: Retrovirus, Picornavirus

Such names are not useful for orderly classification!!!!

These naming conventions can lead to confusion later e.g.: viral hepatitis is caused by at least 6 different viruses

D

“Infectious”

“Serum”

Viral hepatitis

A

NANB

B

Entericallytransmitted

Parenterallytransmitted

E

C

F, G,? Other *

* 10-20% of cases of presumed viral hepatitis are still not accounted for.

Related Herpesviruses Cause Many Different Diseases

• HSV Herpes Simplex Virus Cold sores (type 1),

Genital lesions (type 2)

• VZV Varicella Zoster Virus Chicken pox• CMV Cytomegalovirus Mononucleosis• EBV Epstein-Barr Virus Mononucleosis,

Burkitt’s lymphoma,

• Nasopharyngeal carcinoma

• and HHV-6, HHV-7, HHV-8….. (Human HerpesVirus-#)

Therefore if these viruses were classified based on their symptoms their relationships would be

missed.

Different viruses can cause (nearly) the same symptoms. e.g., the hepatitis viruses

However, different members of the same group can cause different symptoms. e.g., the herpes viruses

Thus,

So virologists had to devise more orderly schemes for classification

Meeting Classification Needs • A universal system of viral classification and a

unified taxonomy was established by the International Committee on Taxonomy of Viruses (ICTV) in 1966. The system makes use of a series of ranked taxons, with the:

• - Order (-virales) being the highest currently recognized.

• - then Family (-viridae) • - Subfamily (-virinae) • - Genus (-virus) • - Species ( eg: tobacco mosaic

virus)

The ICTV seeks input from a wide range of virologists and meets every

three years to revise the taxon.

By the year 2000, over 4000 viruses of plants, animals and bacteria had been included in 71 families, 9 subfamilies and 164 genera.

ICTV Classification Uses a Hierarchical Scheme

(Suffix: viridae)

(Suffix: virus)

(Suffix: virinae)

PoxviridaeHerpesviridaeRetroviridaePicornaviridae

The most important characters are at the top of the Scheme. Other characters are ranked below in order of importance.

This scheme brings order to the classification of viruses irrespective of their hosts or disease symptoms

Primary characteristics used in classification

Viruses are classified according to the nature of their genome and their structure

Genetic material Is Most Important!!!

form of nucleic acid

• ssDNA (+ or - strand)• dsDNA • ssRNA (+ or - strand) • dsRNA • segmented RNA

genetic organization sequence homology

• DNA sequence• • Hybridization

Morphology: by electron microscopy

Secondary characteristics

Replication strategy

Sometimes a group of viruses that seems to be a single group by the above criteria is found to contain a subgroup of viruses which have a fundamentally different replication strategy –

In this case the group will be divided based on the mode of replication.

David Baltimore’s viral genome classification schemeGenomes and strategies of replication most important features for classification. Baltimore originally proposed six different major categories:

Class I: Viruses with double strand DNA genomes. (Adenoviruses)Class II: Viruses with single strand DNA genomes. (Geminiviruses)Class III: Viruses with double strand RNA genomes. (Reoviruses)

Class IV: Plus-sense RNA Viruses. (Picornaviruses)Class V: Viruses with Negative strand RNA genomes. (Rhabdoviruses)Class VI: Viruses with Reverse transcribed RNA genomes. (Retroviruses)We can now add a Seventh Genome Class.Class VII: DNA Genomes replicated by reverse transcription. (Hepatitis B like Pararetroviruses)

RNA Virus Families

Several general features are evident from the classification: None of the dsRNA viruses are enveloped. The minus-strand viruses are enveloped with helical nucleocapsids. Most of the plus-strand strand viruses have icosahedral nucleocapsids. Plus strand viruses vary in having envelopes. Most of the plus strand viruses have a single genomic RNA.

DNA Viruses

DNA Viruses differ in many features from RNA Viruses: Only three families are enveloped. All families except for the poxviruses replicate in nuclei. Many families have very complex nucleocapsids.