Review of Medical Microbiology and Immunology, 13th Edition

31. Classification of Medically Important Viruses

CHAPTER CONTENTS

Principles of Classification

DNA Viruses

Parvoviruses

Polyomaviruses

Papillomaviruses

Adenoviruses

Hepadnaviruses

Herpesviruses

Poxviruses

RNA Viruses

Picornaviruses

Hepeviruses

Caliciviruses

Reoviruses

Flaviviruses

Togaviruses

Retroviruses

Orthomyxoviruses

Paramyxoviruses

Rhabdoviruses

Filoviruses

Coronaviruses

Arenaviruses

Bunyaviruses

Deltavirus

Pearls

Practice Questions: USMLE & Course Examinations

PRINCIPLES OF CLASSIFICATION

The classification of viruses is based on chemical and morphologic criteria. The two major components of the virus used in classification are (1) the nucleic acid (its molecular weight and structure) and (2) the capsid (its size and symmetry and whether it is enveloped). A classification scheme based on these factors is presented in Tables 31–1 and 31–2 for DNA and RNA viruses, respectively. This scheme was simplified from the complete classification to emphasize organisms of medical importance. Only the virus families are listed; subfamilies are described in the chapter on the specific virus.

TABLE 31–1 Classification of DNA Viruses

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TABLE 31–2 Classification of RNA Viruses

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DNA VIRUSES

The families of DNA viruses are described in Table 31–1. The four naked (i.e., nonenveloped) icosahedral virus families—the parvoviruses, polyomaviruses, papillomaviruses, and adenoviruses—are presented in order of increasing particle size, as are the three enveloped families. The hepadnavirus family, which includes hepatitis B virus, and the herpesviruses are enveloped icosahedral viruses. The largest viruses, the poxviruses, have a complex internal symmetry.

Parvoviruses

These are very small (22 nm in diameter), naked icosahedral viruses with single-stranded linear DNA. There are two types of parvoviruses: defective and nondefective. The defective parvoviruses (e.g., adeno-associated virus) require a helper virus for replication. The DNA of defective parvoviruses is unusual because plus-strand DNA and minus-strand DNA are carried in separate particles. The nondefective parvoviruses are best illustrated by B19 virus, which is associated with aplastic crises in sickle cell anemia patients and with erythema infectiosum—an innocuous childhood disease characterized by a “slapped-cheeks” rash.

Polyomaviruses

These are naked icosahedral viruses (45 nm in diameter) with double-stranded circular supercoiled DNA. Two human polyomaviruses are JC virus, isolated from patients with progressive multifocal leukoencephalopathy, and BK virus, isolated from the urine of immunosuppressed kidney transplant patients. Polyomavirus and simian vacuolating virus 40 (SV40 virus) are polyomaviruses of mice and monkeys, respectively, which induce malignant tumors in a variety of species.

Papillomaviruses

Papillomaviruses are naked icosahedral viruses (55 nm in diameter) with double-stranded supercoiled DNA. The human pathogen in the family is human papillomavirus (HPV). It causes papillomas (warts) of many body sites, and certain strains cause carcinoma of the cervix. Many animal species are infected by papillomaviruses, but those viruses are species-specific and do not infect humans.

Adenoviruses

These are naked icosahedral viruses (75 nm in diameter) with double-stranded linear DNA. They cause pharyngitis, upper and lower respiratory tract disease, and a variety of other less common infections. There are at least 40 antigenic types, some of which cause sarcomas in animals but no tumors in humans.

Hepadnaviruses

These are double-shelled viruses (42 nm in diameter) with an icosahedral capsid covered by an envelope. The DNA is a double-stranded circle that is unusual because the complete strand is not a covalently closed circle and the other strand is missing approximately 25% of its length. Hepatitis B virus is the human pathogen in this family.

Herpesviruses

These are enveloped viruses (100 nm in diameter) with an icosahedral nucleocapsid and double-stranded linear DNA. They are noted for causing latent infections. The five important human pathogens are herpes simplex virus types 1 and 2, varicella-zoster virus, cytomegalovirus, and Epstein–Barr virus (the cause of infectious mononucleosis).

Poxviruses

These are the largest viruses, with a bricklike shape, an envelope with an unusual appearance, and a complex capsid symmetry. They are named for the skin lesions, or “pocks,” that they cause. Smallpox virus and molluscum contagiosum virus are the two important members.

RNA VIRUSES

The 14 families of RNA viruses are described in Table 31–2. The three naked icosahedral virus families are listed first and are followed by the three enveloped icosahedral viruses. The remaining eight families are enveloped helical viruses; the first five have single-stranded linear RNA as their genome, whereas the last three have single-stranded circular RNA.

Picornaviruses

These are the smallest (28 nm in diameter) RNA viruses. They have single-stranded, linear, nonsegmented, positive-polarity RNA within a naked icosahedral capsid. The name “picorna” is derived from pico (small), RNA-containing. There are two groups of human pathogens: (1) enteroviruses, such as poliovirus, Coxsackie virus, echovirus, and hepatitis A virus; and (2) rhinoviruses.

Hepeviruses

These are naked viruses (30 nm in diameter) with an icosahedral nucleocapsid. They have single-stranded, linear, nonsegmented, positive-polarity RNA. The main human pathogen is hepatitis E virus.

Caliciviruses

These are naked viruses (38 nm in diameter) with an icosahedral capsid. They have single-stranded, linear, nonsegmented, positive-polarity RNA. The main human pathogen is norovirus.

Reoviruses

These are naked viruses (75 nm in diameter) with two icosahedral capsid coats. They have 10 or 11 segments of double-stranded linear RNA. The name is an acronym of respiratory enteric orphan, because they were originally found in the respiratory and enteric tracts and were not associated with any human disease. The main human pathogen is rotavirus, which causes diarrhea, mainly in infants. The rotavirus genome has 11 segments of double-stranded RNA.

Flaviviruses

These are enveloped viruses with an icosahedral capsid and single-stranded, linear, nonsegmented, positive-polarity RNA. The flaviviruses include hepatitis C virus, yellow fever virus, dengue virus, West Nile virus, and St. Louis and Japanese encephalitis viruses.

Togaviruses

These are enveloped viruses with an icosahedral capsid and single-stranded, linear, nonsegmented, positive-polarity RNA. There are two major groups of human pathogens: the alphaviruses and rubiviruses. The alphavirus group includes eastern and western encephalitis viruses; the rubivirus group consists only of rubella virus.

Retroviruses

These are enveloped viruses with an icosahedral capsid and two identical strands (said to be “diploid”) of single-stranded, linear, positive-polarity RNA. The term retro pertains to the reverse transcription of the RNA genome into DNA. There are two medically important groups: (1) the oncovirus group, which contains the sarcoma and leukemia viruses (e.g., human T-cell leukemia virus [HTLV]); and (2) the lentivirus (“slow virus”) group, which includes human immunodeficiency virus (HIV) and certain animal pathogens (e.g., visna virus). A third group, spumaviruses, is described in Chapter 46.

Orthomyxoviruses

These viruses (myxoviruses) are enveloped, with a helical nucleocapsid and eight segments of linear, single-stranded, negative-polarity RNA. The term myxo refers to the affinity of these viruses for mucins, and ortho is added to distinguish them from the paramyxoviruses. Influenza virus is the main human pathogen.

Paramyxoviruses

These are enveloped viruses with a helical nucleocapsid and single-stranded, linear, nonsegmented, negative-polarity RNA. The important human pathogens are measles, mumps, parainfluenza, and respiratory syncytial viruses.

Rhabdoviruses

These are bullet-shaped enveloped viruses with a helical nucleocapsid and a single-stranded, linear, nonsegmented, negative-polarity RNA. The term rhabdo refers to the bullet shape. Rabies virus is the only important human pathogen.

Filoviruses

These are enveloped viruses with a helical nucleocapsid and single-stranded, linear, nonsegmented, negative-polarity RNA. They are highly pleomorphic, long filaments that are 80 nm in diameter but can be thousands of nanometers long. The term filo means “thread” and refers to the long filaments. The two human pathogens are Ebola virus and Marburg virus.

Coronaviruses

These are enveloped viruses with a helical nucleocapsid and a single-stranded, linear, nonsegmented, positive-polarity RNA. The term corona refers to the prominent halo of spikes protruding from the envelope. Coronaviruses cause respiratory tract infections, such as the common cold and severe acute respiratory syndrome (SARS), in humans.

Arenaviruses

These are enveloped viruses with a helical nucleocapsid and a single-stranded, circular, negative-polarity RNA in two segments. (A part of both segments is positive-polarity RNA, and the term ambisense RNA is used to describe this unusual genome.) The term arena means “sand” and refers to granules on the virion surface that are nonfunctional ribosomes. Two human pathogens are lymphocytic choriomeningitis virus and Lassa fever virus.

Bunyaviruses

These are enveloped viruses with a helical nucleocapsid and a single-stranded, circular, negative-polarity RNA in three segments. Some bunyaviruses contain ambisense RNA in their genome (see Arenaviruses above.) The term bunya refers to the prototype, Bunyamwera virus, which is named after the place in Africa where it was isolated. These viruses cause encephalitis and various fevers such as Korean hemorrhagic fever. Hantaviruses, such as Sin Nombre virus (see Chapter 46), are members of this family.

Deltavirus

Hepatitis delta virus (HDV) is the only member of this genus. It is an enveloped virus with an RNA genome that is a single-stranded, negative-polarity, covalently closed circle. The symmetry of the nucleocapsid is uncertain. It is a defective virus because it cannot replicate unless hepatitis B virus (HBV) is present within the same cell. HBV is required because it encodes hepatitis B surface antigen (HBsAg), which serves as the outer protein coat of HDV. The RNA genome of HDV encodes only one protein, the internal core protein called delta antigen.

PEARLS

• The classification of viruses is based primarily on the nature of the genome and whether the virus has an envelope.

• Poxviruses, herpesviruses, and hepadnaviruses are DNA viruses with an envelope, whereas adenoviruses, polyomaviruses, papillomaviruses, and parvoviruses are DNA viruses without an envelope (i.e., they are naked nucleocapsid viruses). Parvoviruses have single-stranded DNA, whereas all the other families of DNA viruses have double-stranded DNA. The DNA of hepadnaviruses (hepatitis B virus) is mostly double-stranded but has a single-stranded region.

• Picornaviruses, hepeviruses, caliciviruses, and reoviruses are RNA viruses without an envelope, whereas all the other families of RNA viruses have an envelope. Reoviruses have double-stranded RNA; all the other families of RNA viruses have single-stranded RNA. Reoviruses and influenza viruses have segmented RNA; all the other families of RNA viruses have nonsegmented RNA. Picornaviruses, hepeviruses, caliciviruses, flaviviruses, togaviruses, retroviruses, and coronaviruses have positive-polarity RNA, whereas all the other families have negative-polarity RNA.

PRACTICE QUESTIONS: USMLE & COURSE EXAMINATIONS

Questions on the topics discussed in this chapter can be found in the Basic Virology section of PART XIII: USMLE (National Board) Practice Questions starting on page 700. Also see PART XIV: USMLE (National Board) Practice Examination starting on page 731.