Vi

Virology

Viruses infect humans, lower animals, insects, plants, bacteria, and fungi. Classification and nomenclature are standardized by the International Committee on Taxonomy of Viruses through reports published periodically. Viruses are divided into genera and species, as are bacteria; however, most are referred to by common names that have been used for decades. For example, the genera Simplexvirus and Pneumovirus contain herpes simplex and respiratory syncytial viruses, respectively. Viruses of medical importance to humans comprise seven families of DNA viruses and 14 families of RNA viruses (Table 51-1).

general characteristics viral structure

Viruses are composed of a nucleic acid genome surrounded by a protein coat called a capsid. Together the genome and capsid are referred to as the nucleocapsid (Figure 51-1). Genomes are either RNA or DNA. Viral capsids are composed of many individual subunits called capsomeres. Capsomeres assemble into an ico-sahedral or irregular-shaped capsid. Irregular-shaped capsids usually assume a helical form, Icosahedral-shaped capsids are cubical with 20 flat sides, whereas helical capsids are spiral shaped. Some of the larger viruses have a Iipid-containing envelope that surrounds the capsid. In addition, many viruses have glycoprotein spikes that extend from the surface of the virus, acting as attachment projections or as enzymes. The entire virus, including nucleic acid, capsid, envelope, and glycoprotein spikes, is called the virion, or viral particle.

Viruses that cause disease in humans range in size from approximately 20 to 300 nm. Even the largest viruses, such as the poxviruses, cannot be detected with a light microscope, since they are less than one fourth the size of a staphylococcal cell (Figure 51-2).

viral replication

Viruses are stria intracellular parasites, reproducing or replicating only within a host cell. The steps in virus replication, called the infectious cycle, include attachment, penetration, uncoating, macromolecular synthesis, assembly, and release (Figure 51-3).

To initiate the infectious cycle, a virus must first recognize and bind to a suitable host cell, referred to as attachment. Typically, glycoprotein spikes bind to host cell carbohydrate receptors. Viruses recognize and attach to a limited number of host cell types, allowing infection of some tissues but not others. This is referred to as viral tropism.

The process by which viruses enter the host cell is called penetration. One mechanism of penetration involves fusion of the viral envelope with the host cell membrane. Not only does this method internalize the virus but also it can lead to fusion between this and other host cells nearby, forming multinucleated cells called syncytia. The detection of syncytia can be used to identify the presence of virus in cell cultures or stained smears of clinical specimens.

Uncoating occurs once the virus is internalized, Uncoating is necessary to release viral genome before the viral DNA or RNA is delivered to its intracellular site of replication in the nucleus or cytoplasm.

Macromolecular synthesis includes the production of nucleic acid and protein polymers. Viral transcription leads to the synthesis of messenger RNA (mRNA), which encodes early and late viral proteins. Early,, proteins are nonstructural elements, such as enzymes, and late proteins are structural components. Rapid identification of virus in cell culture can be accomplished by-detecting early viral proteins in infected cells using immunofluorescent staining techniques. Replication of viral nucleic acid is necessary to provide genomes for-progeny virions.

During viral assembly, structural proteins, genomes, and, in some cases, viral enzymes are assembled into virions. Envelopes are acquired during viral "budding" from a host cell membrane. Nuclear and cyto| plasmic membranes are common areas for budding-Acquisition of an envelope is the final step in viral assembly.

Release of intact virions occurs following cell lysis or by budding from cytoplasmic membranes. Release by budding may not result in rapid host cell death as does release by lysis. Detection of virus in cell culture is facilitated by recognition of areas of cell lysis. Detection of virus released by budding is more difficult, because the cell monolayer remains intact. Influenza viruses, which are released by budding with minimal cell destruction, can be detected in cell culture by an altera

Table 51 -1 List of DNA and RNA Viruses of Human Importance

DNA Viruses

Family

Viral Members

Adenoviridae

Human adenoviruses

Hepadnaviridae

Hepatitis B virus

Herpesviridae

Herpes simplex virus 1 and 2, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus, human herpes-viruses 6,7, and 8

Papillomaviridae

Human papilloma viruses

Parvovlridae

Parvovirus B-19

Polyomaviridae

BK and JC polyomaviruses

Poxviridae

Variola, vaccinia, orf, molluscum contagiosum, monkeypox

RNA Viruses

Family

Viral Members

Arenaviridas

Lymphocytic choriomeningitis virus, Lassa fever virus

Astroviridae

Gastroenteritis-causing astroviruses

Bunyaviridae

Arboviruses including California encephalitis and Lacrosse viruses; nonarboviruses including sin nombre and related hantaviruses

Caliciviridae

Noroviruses and hepatitis E virus

Coronaviridae

Coronaviruses, including SARS coronavirus

Rloviridae

Ebola and Marburg hemorrhagic fever viruses

Flaviviridae i

Arboviruses including yellow fever, dengue, West Nile, Japanese encephalitis, and St. Louis encephalitis viruses; nonarboviruses including hepatitis C virus

Orthomyxoviridae

Influenza A, B, and C viruses

Paramyxoviridae

Parainfluenza viruses, mumps virus, measles virus, respiratory syncytial virus, metapneumovirus, Nipah virus

Picomaviridae

Polio viruses, coxsackle A viruses, coxsackie B viruses, echoviruses, enteroviruses 68-71, enterovirus 72 (hepatitis A virus), rhinoviruses

Reoviridae

Rotavirus, Colorado tick fever virus

Retroviridae

Human immunodeficiency viruses (HIV-1 and HIV-2), human T-lymphotropic viruses (HTIV-1 and HTLV-2)

Rhabdoviridae

Rabies virus

Togaviridae

Eastern, Western and Venezuela equine encephalitis viruses, rubella virus

native technique called hemadsorption. Influenza virus-infected cells contain virally encoded glycoprotein hemagglutinins that have inserted in the host cell cytoplasmic membrane, preparing for inclusion in the viral envelope at the time of release by cytoplasmic budding. Red blood cells (RBCs) added to the culture medium will adsorb to the outer membranes of infected cells, but not to uninfected cells.

Each infected host cell results in as many as 100,000 virions; however, as few as 1 % of these may be infectious or "viable" in the practical sense. Noninfectious virions result from errors or mutations occurring during the infectious cycle.

classification of viruses

Viruses can be classified according to morphology, type of genome, or means of replication. Morphology in cludes type of capsid, such as icosahedral or irregular. Type of genome includes RNA or DNA, and whether it is single- or double-stranded. Means of replication refers to the strategy each virus uses to duplicate its genome. For example, enteroviruses have single-stranded RNA genomes that synthesize additional strands of RNA directly, whereas retroviruses make RNA in a two-step process by first synthesizing DNA, which subsequently makes RNA. Clinical virologists generally categorize viruses as containing DNA or RNA and further organize by family and common names (see Table 51-1).

viral pathogenesis

Viruses are transmitted from person to person by respiratory, fecal-oral, and sexual contact routes, by trauma or injection with contaminated objects or needles, by tissue transplants (including blood transfusions), by

Figure 51-1 Illustration of viral particle. Enveloped and nonenveloped virions have icosahedral or irregular (usually helical) shape. (Modified from Murray PR, Drew WL, Kobayashi Gs et al, editors: Medical microbiology. Si Louis, 1990, Mosby.)

Icosahedral, nonenveloped virus

Helical, nonenveloped virus

Icosahedral, enveloped virus

Icosahedral, nonenveloped virus

Helical, nonenveloped virus

Icosahedral, enveloped virus

Helical, enveloped virus

^Glycoprotein spikes

Helical, enveloped virus

Human DNA viruses Parvovirus »

Papovavirus $ Adenovirus

Herpesvirus

Poxvirus

Herpesvirus

Poxvirus

Bacteriophage MS2 Bacteriophage M13

Tobacco mosaic virus

Bacteriophage T2

Bacteriophage T2

v/W Chlamydia

Human RNA viruses e Picornavirus f^S Reovirus (o) Togavirus

@ Coronavirus

Orthomyxovirus

£ Rhabdovirus

Paramyxovirus

Escherichia coli 6 pm long

Paramyxovirus

Escherichia coli 6 pm long arthropod or animal bites, and during gestation (transplacental). Once introduced into a host, the virus infects susceptible cells, frequently in the upper respiratory tract. Local infection leads to a viremia (viruses in the blood), which inoculates secondary target tissue distant from the primary site and releases mediators of human immune cell functions. Symptomatic disease ensues. Disease resolves when specific antibody and

Figure 51-2 Relative sizes of representative viruses, bacteriophage (bacterial viruses), and bacteria, including chlamydia. (From Murray PR, Drew WL, Kobayashi GS, et al, editors: Medical microbiology, St Louis, 1990, Mosby.)

cell-mediated immune mechanisms halt continue replication of the virus. Tissue is damaged by lysis of virus-infected cells or by immunopathologic mechanisms directed against the virus but which is also destructive to neighboring tissue. Most DNA-containing viruses, such as those in the herpes group, remain latent host tissue with no observable clinical impact. Reafr tivation may occur accompanying immune suppression^

A viruses navirus irus

/irus lavirus imyxovirus dovirus nyxovirus srichia coli long

Figure 51-3 Illustration of viral infectious cycle. (Modified from Murray PR, Drew WL, Kobayashi GS, et al, editors: Medical microbiology, St Louis, 1990, Mosby.)

(D Virus

Host csll

Attachment

(D Virus

Attachment

Uncoating

(Macromolecuiar synthesis)

transcription

(Macromolecuiar synthesis)

transcription

(Macromolecuiar synthesis)

replication

Figure 51-3 Illustration of viral infectious cycle. (Modified from Murray PR, Drew WL, Kobayashi GS, et al, editors: Medical microbiology, St Louis, 1990, Mosby.)

  • Lysis and / S f ¿ ^ release
  • Macromolecuiar synthesis)

replication

  • Macromolecuiar synthesis) protein synthesis
  • Lysis and / S f ¿ ^ release

Assembly resulting in recurrence of clinically apparent disease. Occasionally, pathogenic viruses stimulate an immune reaction that cross reacts with related human tissue, resulting in damage to host function. This is termed autoimmune pathogenesis and, when present, occurs well after the acute viral infection has resolved. Rare viral infection promotes transformation or immortalization of host cells resulting in uncontrolled cell growth. Viruses with the ability to stimulate uncontrolled growth of host cells are referred to as oncogenic viruses. Some papflloma viruses (wart viruses) are oncogenic, giving rise to human cervical cancer.

Examples of the variety of pathogenic mechanisms shown during viral infection are illustrated by diseases caused by the measles virus. Following replication in the upper respiratory tract and subsequent viremia, the virus infects many susceptible cells throughout the body including endothelial cells in capillaries of the skin. This is accompanied by local inflammation and results in the characteristic rash of measles. Immunocompetent individuals eradicate the virus, resolving their infection, and have lifelong immunity. In some, antibody produced in response to the measles infection cross-reacts with tissue in the central nervous system (CNS), causing a postinfectious encephalitis. In others, slow but continuing replication of damaged virus in the brain gives rise to subacute sclerosing panencephalitis. In those who are severely immunocompromised, ongoing primary infection is not aborted by usual immune mechanisms, resulting in a fatal outcome (Figure 51-4). Measles virus is not an oncogenic virus, thus no cancers result from prolonged infection.

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