Virus (life science)

I

Introduction

Virus (life science), infectious agent found in virtually all life forms, including humans, animals, plants, fungi, and bacteria. Viruses consist of genetic material—either deoxyribonucleic acid (DNA) or ribonucleic acid (RNA)—surrounded by a protective coating of protein, called a capsid, with or without an outer lipid envelope. Viruses are between 20 and 100 times smaller than bacteria and hence are too small to be seen by light microscopy. Viruses vary in size from the largest poxviruses of about 450 nanometers (about 0.000014 in) in length to the smallest polioviruses of about 30 nanometers (about 0.000001 in). Viruses are not considered free-living, since they cannot reproduce outside of a living cell; they have evolved to transmit their genetic information from one cell to another for the purpose of replication.

Viruses often damage or kill the cells that they infect, causing disease in infected organisms. A few viruses stimulate cells to grow uncontrollably and produce cancers. Although many infectious diseases, such as the common cold, are caused by viruses, there are no cures for these illnesses. The difficulty in developing antiviral therapies stems from the large number of variant viruses that can cause the same disease, as well as the inability of drugs to disable a virus without disabling healthy cells. However, the development of antiviral agents is a major focus of current research, and the study of viruses has led to many discoveries important to human health.

II

Structure and Classification

Individual viruses, or virus particles, also called virions, contain genetic material, or genomes, in one of several forms. Unlike cellular organisms, in which the genes always are made up of DNA, viral genes may consist of either DNA or RNA. Like cell DNA, almost all viral DNA is double-stranded, and it can have either a circular or a linear arrangement. Almost all viral RNA is single-stranded; it is usually linear, and it may be either segmented (with different genes on different RNA molecules) or nonsegmented (with all genes on a single piece of RNA).

The viral protective shell, or capsid, can be either helical (spiral-shaped) or icosahedral (having 20 triangular sides). Capsids are composed of repeating units of one or a few different proteins. These units are called protomers or capsomers. The proteins that make up the virus particle are called structural proteins. Viruses also carry genes for making proteins that are never incorporated into the virus particle and are found only in infected cells. These viral proteins are called nonstructural proteins; they include factors required for the replication of the viral genome and the production of the virus particle.

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Capsids and the genetic material (DNA or RNA) they contain are together referred to as nucleocapsids. Some virus particles consist only of nucleocapsids, while others contain additional structures.

Some icosahedral and helical animal viruses are enclosed in a lipid envelope acquired when the virus buds through host-cell membranes. Inserted into this envelope are glycoproteins that the viral genome directs the cell to make; these molecules bind virus particles to susceptible host cells.

The most elaborate viruses are the bacteriophages, which use bacteria as their hosts. Some bacteriophages resemble an insect with an icosahedral head attached to a tubular sheath. From the base of the sheath extend several long tail fibers that help the virus attach to the bacterium and inject its DNA to be replicated and to direct capsid production and virus particle assembly inside the cell.

Viroids and prions are smaller than viruses, but they are similarly associated with disease. Viroids are plant pathogens that consist only of a circular, independently replicating RNA molecule. The single-stranded RNA circle collapses on itself to form a rodlike structure. The only known mammalian pathogen that resembles plant viroids is the deltavirus (hepatitis D), which requires hepatitis B virus proteins to package its RNA into virus particles. Co-infection with hepatitis B and D can produce more severe disease than can infection with hepatitis B alone. Prions are mutated forms of a normal protein found on the surface of certain animal cells. The mutated protein, known as a prion, has been implicated in some neurological diseases such as Creutzfeldt-Jakob disease and Bovine Spongiform Encephalopathy. There is some evidence that prions resemble viruses in their ability to cause infection. Prions, however, lack the nucleic acid found in viruses.

Viruses are classified according to their type of genetic material, their strategy of replication, and their structure. The International Committee on Nomenclature of Viruses (ICNV), established in 1966, devised a scheme to group viruses into families, subfamilies, genera, and species. The ICNV report published in 1995 assigned more than 4000 viruses into 71 virus families. Hundreds of other viruses remain unclassified because of the lack of sufficient information.

III

Replication

The first contact between a virus particle and its host cell occurs when an outer viral structure docks with a specific molecule on the cell surface. For example, a glycoprotein called gp120 on the surface of the human immunodeficiency virus (HIV, the cause of acquired immunodeficiency syndrome, or AIDS) virion specifically binds to the CD4 molecule found on certain human T lymphocytes (a type of white blood cell). Most cells that do not have surface CD4 molecules generally cannot be infected by HIV.

After binding to an appropriate cell, a virus must cross the cell membrane. Some viruses accomplish this goal by fusing their lipid envelope to the cell membrane, thus releasing the nucleocapsid into the cytoplasm of the cell. Other viruses must first be endocytosed (enveloped by a small section of the cell’s plasma membrane that pokes into the cell and pinches off to form a bubblelike vesicle called an endosome) before they can cross the cell membrane. Conditions in the endosome allow many viruses to change the shape of one or more of their proteins. These changes permit the virus either to fuse with the endosomal membrane or to lyse the endosome (cause it to break apart), allowing the nucleocapsid to enter the cell cytoplasm.

Once inside the cell, the virus replicates itself through a series of events. Viral genes direct the production of proteins by the host cellular machinery. The first viral proteins synthesized by some viruses are the enzymes required to copy the viral genome. Using a combination of viral and cellular components, the viral genome can be replicated thousands of times. Late in the replication cycle for many viruses, proteins that make up the capsid are synthesized. These proteins package the viral genetic material to make newly formed nucleocapsids.

To complete the virus replication cycle, viruses must exit the cell. Some viruses bud out of the cell’s plasma membrane by a process resembling reverse endocytosis. Other viruses cause the cell to lyse, thereby releasing newly formed virus particles ready to infect other cells. Still other viruses pass directly from one cell into an adjacent cell without being exposed to the extracellular environment. The virus replication cycle can be as short as a couple of hours for certain small viruses or as long as several days for some large viruses.

Some viruses kill cells by inflicting severe damage resulting in cell lysis; other viruses cause the cell to kill itself in response to virus infection. This programmed cell suicide is thought to be a host defense mechanism to eliminate infected cells before the virus can complete its replication cycle and spread to other cells. Alternatively, cells may survive virus infection, and the virus can persist for the life of its host. Virtually all people harbor harmless viruses.

Retroviruses, such as HIV, have RNA that is transcribed into DNA by the viral enzyme reverse transcriptase upon entry into the cell. (The ability of retroviruses to copy RNA into DNA earned them their name because this process is the reverse of the usual transfer of genetic information, from DNA to RNA.) The DNA form of the retrovirus genome is then integrated into the cellular DNA and is referred to as the provirus. The viral genome is replicated every time the host cell replicates its DNA and is thus passed on to daughter cells.

Hepatitis B virus can also transcribe RNA to DNA, but this virus packages the DNA version of its genome into virus particles. Unlike retroviruses, hepatitis B virus does not integrate into the host cell DNA.

IV

Disease

Most viral infections cause no symptoms and do not result in disease. For example, only a small percentage of individuals who become infected with Epstein-Barr virus or western equine encephalomyelitis virus ever develop disease symptoms. In contrast, most people who are infected with measles, rabies, or influenza viruses develop the disease. A wide variety of viral and host factors determine the outcome of virus infections. A small genetic variation can produce a virus with increased capacity to cause disease. Such a virus is said to have increased virulence.

Viruses can enter the body by several routes. Herpes simplex virus and poxviruses enter through the skin by direct contact with virus-containing skin lesions on infected individuals. Ebola, hepatitis B, and HIV can be contracted from infected blood products. Hypodermic needles and animal and insect bites can transmit a variety of viruses through the skin. Viruses that infect through the respiratory tract are usually transmitted by airborne droplets of mucus or saliva from infected individuals who cough or sneeze. Viruses that enter through the respiratory tract include orthomyxovirus (influenza), rhinovirus and adenovirus (common cold), and varicella-zoster virus (chicken pox). Viruses such as rotavirus, coronavirus, poliovirus, hepatitis A, and some adenoviruses enter the host through the gastrointestinal tract. Sexually transmitted viruses, such as herpes simplex, HIV, and human papilloma viruses (HPV), gain entry through the genitourinary route. Other viruses, including some adenoviruses, echoviruses, Coxsackie viruses, and herpesviruses, can infect through the eye.

Virus infections can be either localized or systemic. The path of virus spread through the body in systemic infections differs among different viruses. Following replication at the initial site of entry, many viruses are spread to their target organs by the bloodstream or the nervous system.

The particular cell type can influence the outcome of virus infection. For example, herpes simplex virus undergoes lytic replication in skin cells around the lips but can establish a latent or dormant state in neuron cell bodies (located in ganglia) for extended periods of time. During latency, the viral genome is largely dormant in the cell nucleus until a stimulus such as a sunburn causes the reactivation of latent herpesvirus, leading to the lytic replication cycle. Once reactivated, the virus travels from the ganglia back down the nerve to cause a cold sore on the lip near the original site of infection. The herpesvirus genome does not integrate into the host cell genome.

Virus-induced illnesses can be either acute, in which the patient recovers promptly, or chronic, in which the virus remains with the host or the damage caused by the virus is irreparable. For most acute viruses, the time between infection and the onset of disease can vary from three days to three weeks. In contrast, onset of AIDS following infection with HIV takes an average of 7 to 11 years.

Several human viruses are likely to be agents of cancer, which can take decades to develop. The precise role of these viruses in human cancers is not well understood, and genetic and environmental factors are likely to contribute to these diseases. But because a number of viruses have been shown to cause tumors in animal models, it is probable that many viruses have a key role in human cancers.

Some viruses—alphaviruses and flaviviruses, for example—must be able to infect more than one species to complete their life cycles. Eastern equine encephalomyelitis virus, an alphavirus, replicates in mosquitoes and is transmitted to wild birds when the mosquitoes feed. Thus, wild birds and perhaps mammals and reptiles serve as the virus reservoir, and mosquitoes serve as vectors essential to the virus life cycle by ensuring transmission of the virus from one host to another. Horses and people are accidental hosts when they are bitten by an infected mosquito, and they do not play an important role in virus transmission.

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