Classification of Viruses

Classification of Viruses
Basis of Classification
The following properties have been used as a basis for the classification of viruses:
(1) Virion morphology, including size, shape, type of symmetry, presence or absence of peplomers, and presence or absence of membranes.
(2) Virus genome properties, including type of nucleic acid (DNA or RNA), size of genome in kilobases (kb) , strandedness (single or double), whether linear or circular, sense (positive, negative), segments (number, size), nucleotide sequence and G + C content.
(3) Physicochemical properties of the virion, including molecular mass, pH stability, thermal stability, and susceptibility to physical and chemical agents, especially ether and detergents.
(4) Virus protein properties, including number, size, and functional activities of structural and nonstructural proteins, amino acid sequence, and modifications (glycosylation, phosphorylation).
(5) Genome organization and replication, including gene order, number and position of open reading frames, strategy of replication (patterns of transcription, translation), and cellular sites (accumulation of proteins, virion assembly, virion release).
(6) Antigenic properties.
(7) Biologic properties, including natural host range, mode of transmission, vector relationships, pathogenicity, tissue tropisms, and pathology.
Classification Systems
They are four types of classification system can be summarized as follow :
1- ICTV classification
The International Committee on Taxonomy of Viruses (ICTV) developed the current classification system and put a greater certain virus properties to maintain family uniformity. The general taxonomic structure is as follows:
Order (-virales)
Family (-viridae)
Subfamily (-virinae)
Genus (-virus)
Species (-virus)
This classification system does not formally distinguish between subspecies, strains, and isolates.
2- Baltimore classification
The Baltimore classification of viruses is based on the method of viral mRNA synthesis.




Figure 1: Baltimore Classification of viruses
The Nobel Prize-winning biologist David Baltimore devised the Baltimore classification system. The ICTV classification system is used in conjunction with the Baltimore classification system in modern virus classification.
The Baltimore classification of viruses is based on the mechanism of mRNA production. Viruses must generate mRNAs from their genomes to produce proteins and replicate themselves, but different mechanisms are used to achieve this in each virus family. Viral genomes may be single-stranded (ss) or double-stranded (ds), RNA or DNA, and may or may not use reverse transcriptase (RT). In addition, ssRNA viruses may be either sense (+) or antisense (?). This classification places viruses into seven groups as above.
As an example of viral classification, the chicken pox virus, varicella zoster (VZV), belongs to the order Herpesvirales, family Herpesviridae, subfamily Alphaherpesvirinae, and genus Varicellovirus. VZV is in Group I of the Baltimore Classification because it is a dsDNA virus that does not use reverse transcriptase.
DNA viruses
• Group I: viruses possess double-stranded DNA.
• Group II: viruses possess single-stranded DNA.
Table 1: Examples of DNA viruses
Virus Family Examples (common names) Virion
naked/enveloped Capsid
Symmetry Nucleic acid type Group
1.Adenoviridae
Adenovirus, hepatitis virus Naked Icosahedral ds I
2.Papillomaviridae
Papillomavirus Naked Icosahedral ds circular I
3.Parvoviridae
Parvovirus B19, Canine parvovirus Naked Icosahedral ss II
4.Herpesviridae
Herpes simplex virus, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus Enveloped Icosahedral ds I
5.Poxviridae
Smallpox virus, cow pox virus, sheep pox virus, orf virus, monkey pox virus, vaccinia virus Complex coats Complex ds I
6.Hepadnaviridae
Hepatitis B virus Enveloped Icosahedral circular, partially ds VII
7.Polyomaviridae
Polyoma virus; JC virus (progressive multifocal leukoencephalopathy) Naked Icosahedral ds circular I
8.Anelloviridae
Torque teno virus Naked Icosahedral ss circular II

RNA viruses
• Group III: viruses possess double-stranded RNA genomes
• Group IV: viruses possess positive-sense single-stranded RNA genomes. Group V: viruses possess negative-sense single-stranded RNA genomes

Table 2: Examples of RNA viruses
Virus Family Examples (common names) Capsid naked/enveloped Capsid
Symmetry Nucleic acid type Group
1.Reoviridae
Reovirus, Rotavirus
Naked Icosahedral ds III
2.Picornaviridae
Enterovirus, Rhinovirus, Hepatovirus, Cardiovirus, Aphthovirus, Poliovirus, Parechovirus, Erbovirus, Kobuvirus, Teschovirus, Coxsackie
Naked Icosahedral ss IV
3.Caliciviridae
Norwalk virus, Hepatitis E virus
Naked Icosahedral ss IV
4.Togaviridae
Rubella virus
Enveloped Icosahedral ss IV
5.Arenaviridae
Lymphocytic choriomeningitis virus
Enveloped Complex ss(-) V
6.Flaviviridae
Dengue virus, Hepatitis C virus, Yellow fever virus
Enveloped Icosahedral ss IV
7.Orthomyxoviridae
Influenzavirus A, Influenzavirus B, Influenzavirus C, Isavirus, Thogotovirus
Enveloped Helical ss(-) V
8.Paramyxoviridae
Measles virus, Mumps virus, Respiratory syncytial virus, Rinderpest virus, Canine distemper virus
Enveloped Helical ss(-) V
9.Bunyaviridae
California encephalitis virus, Hantavirus
Enveloped Helical ss(-) V
10.Rhabdoviridae
Rabies virus
Enveloped Helical ss(-) V
11.Filoviridae
Ebola virus, Marburg virus
Enveloped Helical ss(-) V
12.Coronaviridae
Corona virus
Enveloped Helical ss IV
13.Astroviridae
Astrovirus
Naked Icosahedral ss IV
14.Bornaviridae
Borna disease virus
Enveloped Helical ss(-) V
15.Arteriviridae
Arterivirus, Equine Arteritis Virus
Enveloped Icosahedral ss IV
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.
3- Holmes classification
Holmes (1948) used Carolus Linnaeus s system of binomial nomenclature to classify viruses into 3 groups under one order, Virales. They are placed as follows:
• Group I: Phaginae (attacks bacteria)
• Group II: Phytophaginae (attacks plants)
• Group III: Zoophaginae (attacks animals)
4- LHT System of Virus Classification
The LHT System of Virus Classification is based on chemical and physical characters like nucleic acid (DNA or RNA), Symmetry (Helical or Icosahedral or Complex), presence of envelope, diameter of capsid, number of capsomers. This classification was approved by the Provisional Committee on Nomenclature of Virus (PNVC) of the International Association of Microbiological Societies (1962).
VIRUS REPLICATION
Steps in Viral Replication
Viral populations do not grow through cell division, because they are a cellular. Instead, they use the machinery and metabolism of a host cell to produce multiple copies of themselves, and they assemble in the cell.
The following steps take place during viral replication;-
1. Adsorption
2. Penetration
3. Uncoating
4. Viral genome replication
5. Maturation
6. Release

Figure 3: Replication cycle
1. Adsorption
The virus becomes attached to the cells, and at this stage, it can be recovered in the infectious form without cell lysis by procedures that either destroy the receptors or weaken their bonds to the virions. Animal viruses have specialized attachment sites distributed over the surface of the virion e.g. orthomyxoviruses and paramyxoviruses attach through glycoprotein spikes, and adenoviruses attach through the penton fibers. Adsorption occurs to specific cellular receptors. Some receptors are glycoproteins, others are phospholipids or glycolipids.
2. Penetration
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. the process by which many hormones and toxins enter cells.
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. Viral Nucleic Acid 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.
5-Maturation and Release
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. Some viruses undergo a lysogenic cycle where the viral genome is incorporated by genetic recombination into a specific place in the host s chromosome. 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; however, 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.
DNA viruses
The genome replication of most DNA viruses takes place in the cell s nucleus. except poxviruses which replicate in the cytoplasm.
RNA viruses
Replication usually takes place in the cytoplasm. except retroviruses , influenza virus and hepatitis virus which replicate in the nucleus .

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.



Antiviral Chemotherapy
There is a need for antiviral drugs active against viruses for which vaccines are not available or not highly effective. Antivirals are needed to reduce morbidity and economic loss due to viral infections and to treat increasing numbers of immunosuppressed patients who are at increased risk of infection.
Types of antiviral drugs:
* Nucleoside Analogs
The majority of available antiviral agents are nucleoside analogs. They inhibit nucleic acid replication by inhibition of polymerases for nucleic acid replication. In addition, some analogs can be incorporated into the nucleic acid and block further synthesis or alter its function.
* Nucleotide Analogs
Nucleotide analogs differ from nucleoside analogs in having an attached phosphate group. Their ability to persist in cells for long periods of time increases their potency. Cidofovir is an example.
* Nonnucleoside Reverse Transcriptase Inhibitors
Nevirapine was the first member of the class of nonnucleoside reverse transcriptase inhibitors. It does not require phosphorylation for activity and does not compete with nucleoside triphosphates. It acts by binding directly to reverse transcriptase and disrupting the enzyme s catalytic site.
* Protease Inhibitors
Saquinavir was the first protease inhibitor to be approved for treatment of HIV infection. Such drugs inhibit the viral protease that is required at the late stage of the replicative cycle to cleave the viral polypeptide precursors to form the mature virion core and activate the reverse transcriptase that will be used in the next round of infection. Protease inhibitors include indinavir and ritonavir .
* Fusion Inhibitor
Fuzeon is a large peptide that blocks the virus and cellular membrane fusion step involved in entry of HIV-1 into cells.

Other Types of Antiviral Agents
* Amantadine and Rimantadine
These synthetic amines specifically inhibit influenza A viruses by blocking viral uncoating.
* Foscarnet (Phosphonoformic Acid, PFA)
Foscarnet, an organic analog of inorganic pyrophosphate, selectively inhibits viral DNA polymerases and reverse transcriptases at the pyrophosphate-binding site.
* Methisazone
Methisazone is of historical interest as an inhibitor of poxviruses. It blocked a late stage in viral replication, resulting in the formation of immature, noninfectious virus particles.
Table 3: Examples of Antiviral Compounds Used for Treatment of Viral Infections.

Drug Nucleoside Analog Mechanism of Action Viral Spectrum

Acyclovir Yes Viral polymerase inhibitor Herpes simplex, varicella-zoster
Amantadine No Blocks viral uncoating Influenza A
Cidofovir No Viral polymerase inhibitor Cytomegalovirus, herpes simplex, polyomavirus
Didanosine (ddI) Yes Reverse transcriptase inhibitor HIV-1, HIV-2
Foscarnet No Viral polymerase inhibitor Herpesviruses, HIV-1, HBV
Fuzeon No HIV fusion inhibitor (blocks viral entry) HIV-1
Ganciclovir Yes Viral polymerase inhibitor Cytomegalovirus
Indinavir No HIV protease inhibitor HIV-1, HIV-2
Lamivudine (3TC) Yes Reverse transcriptase inhibitor HIV-1, HIV-2, HBV
Nevirapine No Reverse transcriptase inhibitor HIV-1
Ribavirin Yes Perhaps blocks capping of viral mRNA Respiratory syncytial virus, influenza A and B, Lassa fever, hepatitis C, others
Ritonavir No HIV protease inhibitor HIV-1, HIV-2
Saquinavir No HIV protease inhibitor HIV-1, HIV-2
Stavudine (d4T) Yes Reverse transcriptase inhibitor HIV-1, HIV-2
Trifluridine Yes Viral polymerase inhibitor Herpes simplex, cytomegalovirus, vaccinia
Valacyclovir Yes Viral polymerase inhibitor Herpesviruses
Vidarabine Yes Viral polymerase inhibitor Herpesviruses, vaccinia, HBV
Zalcitabine (ddC) Yes Reverse transcriptase inhibitor HIV-1, HIV-2, HBV
Zidovudine (AZT) Yes Reverse transcriptase inhibitor HIV-1, HIV-2, HTLV-1

Interferons
Interferons (IFNs) are host-coded proteins that are members of the large cytokine family and which inhibit viral replication. They are produced very quickly (within hours) in response to viral infection or other inducers and are one of the body s first responders in the defense against viral infection. Interferons are central to the innate antiviral immune response. They also modulate humoral and cellular immunity and have broad cell growth regulatory activities.
Properties of Interferons
There are multiple species of interferons that fall into three general groups as follow:
Table 4: Properties of Human Interferons.


Property Type
Alpha Beta Gamma
Current nomenclature IFN-? IFN-? IFN-?
Former designation Leukocyte Fibroblast Immune interferon
Type designation Type I Type I Type II
Number of genes that code for family 20 1 1
Principal cell sour
e Most cell types Most cell types Lymphocytes
Inducing agent Viruses; dsRNA Viruses; dsRNA Mitogens
Stability at pH 2.0 Stable Stable Labile
Introns in genes No No Yes
Chromosomal location of genes 9 9 12
Size of secreted protein (number of amino acids) 165 166 143
Chromosomal location of IFN receptor genes 21 21 6

Viral Vaccines
The purpose of viral vaccines is to utilize the immune response of the host to prevent viral disease. Several vaccines have proved to be effective at reducing the incidence of viral disease Vaccination is the most cost-effective method of prevention of serious viral infections.


Table 5: Comparison of Characteristics of Killed and Live Viral Vaccines

Characteristic Killed Vaccine Live Vaccine
Number of doses Multiple Single
Need for adjuvant Yes No
Duration of immunity Shorter Longer
Effectiveness of protection (more closely mimics natural infection) Lower Greater
Immunoglobulins produced IgG IgA and IgG
Mucosal immunity produced Poor Yes
Cell-mediated immunity produced Poor Yes
Residual virulent virus in vaccine Possible No
Reversion to virulence No Possible
Excretion of vaccine virus and transmission to nonimmune contacts No Possible
Interference by other viruses in host No Possible
Stability at room temperature High Low