Virus types

Definition

Viruses are intracellular, parasitic, pathogenic organisms that consist of either deoxyribonucleic acid (DNA) or ribonucleic acid (RNA), either of which can be single-stranded or double-stranded depending on the virus type. Both types are surrounded by a protein coat called the capsid; the combination of genome and capsid is referred to as the nucleocapsid. Some viruses also have an outer lipid envelope with embedded spikes acquired by budding through a cellular membrane.

Classification

The morphology (physical shape) of the virus particle represents one broad category of viral classification. Most viruses are limited in the quantity of genetic material they encode. Consequently, the most efficient means to encode the proteins that will be used for the capsid is to utilize repeating protein units known as protomers, which can self-assemble into the subunits, or capsomeres, of the capsid. The result of utilizing repeating units is that the morphological symmetry will be one of two forms: icosahedral (cuboidal) and helical. The only exception is found among the large poxviruses that can encode more than two hundred proteins, allowing for a significantly greater complexity of structure.

Helical capsids resemble long hollow tubes in which the genome is in the center. Capsomeres are arranged in a helical fashion around the core. All known helical viruses contain RNA as the genetic material. The helical nucleocapsid for some viruses, such as rabies, measles, and influenza, is enclosed within a viral envelope. Icosahedral viruses have twenty faces, each an equilateral triangle, and twelve corners or vertices. Icosahedral viruses include the papilloma (wart) viruses, poliovirus, rhinovirus (which causes the common cold), and herpesvirus. The herpesviruses also contain an external envelope.

The host range of the virus, or the species the virus can infect, is determined by proteins on the surface of the virus (the capsid on nonenveloped viruses or the spikes on enveloped particles) and viral receptors on the surface of the host cell. Many viruses are species-specific: Human rhinoviruses, measles, and herpesviruses infect humans only, for example. In some cases, however, different species share common types of receptors, which explains why certain viruses, such as influenza and rabies, can cross species lines. Likewise, viruses may exhibit specific cell tropisms within the species, infecting only those tissues that express certain receptors. Influenza is a respiratory virus and does not infect other tissues; the popular term "stomach flu" is a misnomer because it involves neither the influenza virus nor the stomach.

Viral Genomes

The disadvantage of classifying viruses on the basis of morphology is the failure of this method to take into account evolutionary relationships. Viruses that are closely related genetically may produce radically different pathologies; respiratory viruses like the rhinoviruses are genetically related to poliovirus and hepatitis A virus, even though the methods of transmission and the sites of infection differ.

In the early 1970s, David Baltimore, then a virologist at the Massachusetts Institute of Technology, proposed a method of classification in which virus families were grouped according to the structure and replication strategy of the genome. Viruses within the same class generally shared a genetic relationship, even though their pathologies differed. Baltimore proposed six classes: double-stranded or single-stranded DNA, classes I and II respectively; double-stranded RNA (class III); single-stranded RNA of positive (+) polarity (class IV); single-stranded RNA of negative (-) polarity (class V); and RNA viruses, which replicate through a DNA intermediate (class VI). Class VII was later added, representing double-stranded DNA viruses that use an RNA intermediate. The positive and negative polarities refer not to any charge, but to the orientation of the genome with respect to messenger RNA (mRNA). mRNA is defined as being a positive strand. Genomes that are positive-stranded are identical to the mRNA, while negative-stranded genomes are complementary to mRNA.

Within each class, viruses are grouped in subcategories of families in which the suffix viridae denotes a family. For example, all herpesviruses are within the family Herpesviridae. The viral genus is denoted by the suffix virus, as in “rhinovirus” or “herpesvirus.” The Baltimore classes are as follows:

Class I: Double-stranded DNA viruses. These include both nonenveloped viruses (Polyomaviridae, Papillomaviridae, and Adenoviridae) and two enveloped families (Herpesviridae and Poxviridae). The polyomaviruses that make up the family are highly species-specific, and most are not associated with human infections. The ability of several members of this family to cause neoplastic changes, or cancers, in cultured cells has led to extensive research into mechanisms of cell regulation. There is no evidence, however, that these viruses pose a threat to humans. One member of the family in particular, simian virus 40 (SV40), generated concern because it was a contaminant in early poliovirus vaccines grown in rhesus monkey cells; no evidence has been found to suggest the virus poses a threat to humans. However, two variants of the SV40 virus, JC virus and BK virus, are associated with rare neurological disease in immunocompromised persons.

The Papillomaviridae are well known as the etiological agents of human warts. More than one hundred serotypes of the human papilloma virus (HPV) are known, the vast majority causing only benign growths called condylomas (warts). Because genital HPV is so common, genital warts represent one of the most common types of sexually transmitted diseases. About one dozen HPV serotypes, however, are capable of malignant transformation of cervical cells, resulting in cervical cancer, one of the leading causes of cancer deaths in women. Gardisil, the cervical cancer vaccine, is a quadrivalent vaccine directed against the four most common HPV serotypes associated with cervical cancer.

The Adenoviridae, or adenoviruses, are associated with respiratory infections in humans. More than one hundred serotypes are known, about one-half of which are associated with human infections. In the majority of cases, infections appear in children as either a mild infection or an illness associated with sore throats or fever, or both.

The Herpesviridae family includes eight known types of human herpesviruses (HHV). While the illnesses associated with these viruses vary, all exhibit latency in which following recovery the infected person harbors the virus in a nonreplicative state for the remainder of their life. The virus may periodically become reactivated in some people, resulting in illness that may be mild to severe. The best known of these viruses include HHV-1,2, often called herpes simplex types 1 and 2, which are associated with cold sores. HHV-3, or varicella zoster virus, is the agent of chickenpox. Reactivation of the virus from a latent state results in the localized rash known as shingles. HHV-4, the Epstein-Barr virus (EBV), is associated with infectious mononucleosis. EBV has generated significant research, as it is also a potential cancer virus, the etiological agent of Burkitt’s lymphoma and nasopharyngeal carcinoma, and possibly the etiological agent of Hodgkin’s disease.

The largest group morphologically of double-stranded DNA viruses are the poxviruses. It is estimated that variola (smallpox) virus killed an estimated 400,000 persons annually in Europe before the development of an effective vaccine by English physician Edward Jenner. Smallpox was the first viral disease eradicated from human civilization, the result of an effective vaccination campaign in the 1970s.

Class II: Single-stranded DNA viruses. The Parvoviridae (parvo means “small”) contain linear single-stranded DNA genomes. The only parvovirus known to be associated with human disease is B19, the etiological agent for erythema infectiosum, or fifth disease, a common rash in children.

Class III: Double-stranded RNA viruses. The only family of double-stranded RNA animal viruses are the Reoviridae (“reo” stands for “respiratory enteric orphan”). The name originally reflected its isolation from both the gastrointestinal and respiratory tracts and the mistaken belief that it was of no clinical significance. The evolution of the original classification of reovirus as an enteric virus to its own family reflected the increasing role of molecular biology in the study of viruses during the 1960s. The virus was later discovered to contain a distinctive genome, both double-stranded and existing in the form of ten to twelve segments. Reoviruses are nonenveloped viruses, with a double-layered icosahedral capsid.

Most members of the family cause no significant clinical disease. The most important pathogen is rotavirus, arguably one of the most important causes of gastrointestinal disease in young children. Estimates hold that nearly 100 percent of children worldwide are infected early in childhood, with some one-half million deaths, caused primarily by the combination of severe diarrhea and poor health care throughout much of the world.

Class IV: Single-stranded, positive-stranded RNA viruses. Four major families are placed in this class, two icosahedral nonenveloped families (Picornaviridae, or picornaviruses, and Caliciviridae) and two families on enveloped icosahedral viruses (Togaviridae and Coronaviridae).

The term “picornavirus” refers to a “small” (pico) RNA virus. These viruses include the first animal virus discovered (foot-and-mouth-disease virus) and polioviruses, hepatitis A virus, and rhinoviruses, which are associated with the common cold. The development of the first Salk vaccine and, subsequently, of the Sabin oral vaccine for the prevention of poliomyelitis have ranked among the most important developments in the control of infectious disease. From its peak annual incidence of greater than fifty thousand cases of polio in the United States in the early 1950s, the disease was largely eradicated worldwide by the twenty-first century, with only a few pockets of infection remaining in developing countries. The rhinoviruses, which include more than 120 serotypes, are the etiological agents for most colds. The existence of many serotypes is the primary reason that people average two to three colds each year until well into the adult years.

The term "hepatitis" refers to a clinical condition and is associated with infection by several different, and unrelated, types of viruses. Hepatitis A virus, like poliovirus and several other types of picornaviruses, is transmitted through a fecal-oral route and begins as a gastrointestinal infection.

The caliciviruses (calyx- or cup-shaped structures on the viral surface) include the norovirus (Norwalk virus), which is among the most common causes of gastroenteritis in adults. The Norwalk virus is frequently the cause of intestinal illnesses on cruise ships, in schools, and in nursing homes.

The togaviruses, named for the toga or coat appearance of the envelope, include primarily arthropod-borne viruses such as those associated with viral encephalitis, yellow fever, West Nile virus, and hepatitis C virus. Yellow fever was the first viral disease demonstrated to be transmitted by mosquitoes. The building of the Panama Canal during the first decade of the twentieth century was made possible in large part by the Walter Reed Commission’s program for control of mosquitoes in Cuba and Panama. Not all togaviruses are arthropod-borne, however. Rubella virus, associated with German measles, is a respiratory transmitted virus classified within the togaviruses because of its molecular similarity.

The coronaviruses contain a single RNA genome that is the largest known among the RNA viruses. Human infections are relatively common, probably second only to those caused by rhinoviruses, and they often result in symptoms resembling those of the common cold. Many are believed to originate in bats, and some can cause serious complications in humans. The diseases known as SARS (severe acute respiratory syndrome), identified in early 2003, and MERS (Middle East respiratory syndrome), first identified in 2012, represent unusually virulent strains of the virus. Even more disruptive from a public health standpoint was the coronavirus 2019 (COVID-19) outbreak that reached pandemic level in early 2020 due to its ease of transmission from human to human.

Class V: Single-stranded, negative-stranded RNA viruses. The negative-stranded RNA viruses include four major enveloped families: Orthomyxoviridae (influenza viruses), Paramyxoviridae (measles, mumps), Filoviridae (Ebola virus), and Rhabdoviridae (rabies). Only the myxoviruses have segmented genomes.

The myxoviruses (myxa or mucus) include all the influenza viruses. The type of influenza (A, B, and C) refers to the proteins of the nucleocapsid: Type A is the most common cause of epidemics. The viral envelope includes two types of spikes: the hemagglutinin (H) protein, which is used to attach to the target cell, and the neuraminidase (N), which is used for release from the cell. The particular strain of the virus is indicated by one of the sixteen types of H protein and nine types of N protein. For example, the 2009 swine influenza pandemic was the H1N1 type. Because the genome of influenza viruses is segmented, coinfection of cells by different strains of the virus may result in reassortment of segments, creating an entirely new strain, as happened with the swine influenza virus.

Measles virus is similar to those viruses that cause illnesses in animals: distemper and rinderpest viruses. Genetic analysis has suggested all three viruses originated from a common ancestor, and humans became infected from cross-species infection and adaptation as animals were domesticated.

The filoviruses include the Marburg virus, discovered in Marburg, Germany, in 1967 when workers were infected from handling monkey tissue, and the Ebola virus, discovered following an outbreak near the Ebola River in northern Congo. Both viruses cause life-threatening hemorrhagic fevers.

Class VI: RNA viruses with DNA intermediate. The Retroviridae or retroviruses contain a positive-stranded RNA but replicate through a DNA intermediate. Following infection, the RNA is copied by a viral reverse transcriptase into a double-stranded DNA, which is then integrated into the host genome. Expression of the viral genes and production of progeny virus utilizes only the integrated "provirus."

Three subclasses of retroviruses are known: RNA tumor viruses, originally discovered by Peyton Rous early in the twentieth century; lentiviruses (slow viruses, reflecting the slow progression of disease) such as human immunodeficiency virus (HIV); and "foamy" viruses, which are not associated with any known human disease.

The RNA tumor viruses were critical in the discovery of the role played by oncogenes in creating cancer cells, but with few exceptions, they are not associated with human cancers. Those viruses that are, such as human T-cell lymphotropic viruses (HTLV-1,2), do not actually kill the cell but disrupt regulation. HIV, the agent of acquired immunodeficiency syndrome, ultimately kills the infected cell. Because the target cell, the T lymphocyte, is critical to the regulation of the immune response, the result is a complete breakdown of the immune system. HIV likely originated from similar viruses in chimpanzees that jumped species and became adapted to humans.

Class VII: DNA retroviruses. A later addition to the Baltimore classification system, the Hepadnaviridae (hepatitis DNA viruses), contain a double-stranded DNA genome that replicates using an RNA intermediate. The RNA is generated using a cellular RNA polymerase that copies the viral genome. In turn, the RNA is copied by a viral reverse transcriptase into progeny DNA.

The most important member of the group is hepatitis B virus, the primary cause of severe viral liver disease and of hepatocellular carcinoma, or liver cancer. As many as 2 billion persons worldwide are believed to have been infected (290 million chronically) with the virus, which causes nearly 820,000 deaths annually, according to the Hepatitis B Foundation.

Impact

The ability to sequence the genomes of an increasing number of viruses has led to an understanding of the phylogenetic relationships among these organisms, despite the seemingly unrelated array of diseases with which they are associated. Viruses within the same family have been shown to share common ancestry. Among the questions that can be addressed is that of the origin of human viruses, many of which began as zoonotic diseases in other animals. As human civilization began to encroach into new animal habitats and began the domestication of animals such as dogs and ruminants (cattle and sheep), viruses adapted to new hosts. The process continues, as virus infections associated with newly discovered agents such as Ebola virus, hantavirus, novel coronaviruses, and even HIV have moved from nonhuman hosts, such as rodents and nonhuman primates, into the human population.

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