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Overview of Viruses
Viruses are the smallest parasites, typically ranging from 0.02 to 0.3 μm, although several very large viruses up to 1 μm long (megavirus, pandoravirus) have recently been discovered. Viruses depend completely on cells (bacterial, plant, or animal) to reproduce. Viruses have an outer cover of protein and sometimes lipid, an RNA or DNA core, and sometimes enzymes needed for the first steps of viral replication.
Viruses are classified principally according to the nature and structure of their genome and their method of replication, not according to the diseases they cause. Thus, there are DNA viruses and RNA viruses; each type may have single or double strands of genetic material. Single-strand RNA viruses are further divided into those with (+) sense and (-) sense RNA. DNA viruses typically replicate in the host cell nucleus, and RNA viruses typically replicate in the cytoplasm. However, certain single-strand, (+) sense RNA viruses termed retroviruses use a very different method of replication.
Retroviruses use reverse transcription to create a double-stranded DNA copy (a provirus) of their RNA genome, which is inserted into the genome of their host cell. Reverse transcription is accomplished using the enzyme reverse transcriptase, which the virus carries with it inside its shell. Examples of retroviruses are the human immunodeficiency viruses and the human T-cell leukemia viruses. Once the provirus is integrated into the host cell DNA, it is transcribed using typical cellular mechanisms to produce viral proteins and genetic material. If the infected cell belongs to the germline, the integrated provirus can become established as an endogenous retrovirus that is transmitted to offspring. The sequencing of the human genome revealed that at least 1% of the human genome consists of endogenous retroviral sequences, representing past encounters with retroviruses during the course of human evolution. A few endogenous human retroviruses have remained transcriptionally active and produce functional proteins (eg, the syncytins that contribute to the structure of the human placenta). Some experts speculate that some disorders of uncertain etiology, such as multiple sclerosis, certain autoimmune disorders, and various cancers, may be caused by endogenous retroviruses.
Because RNA transcription does not involve the same error-checking mechanisms as DNA transcription, RNA viruses, particularly retroviruses, are particularly prone to mutation.
For infection to occur, the virus first attaches to the host cell at one or one of several receptor molecules on the cell surface. The viral DNA or RNA then enters the host cell and separates from the outer cover (uncoating) and replicates inside the host cell in a process that requires specific enzymes. The newly synthesized viral components then assemble into a complete virus particle. The host cell typically dies, releasing new viruses that infect other host cells. Each step of viral replication involves different enzymes and substrates and offers an opportunity to interfere with the process of infection.
The consequences of viral infection vary considerably. Many infections cause acute illness after a brief incubation period, but some are asymptomatic or cause minor symptoms that may not be recognized except in retrospect. Many viral infections are cleared by the body’s defenses, but some remain in a latent state, and some cause chronic disease. In latent infection, viral RNA or DNA remains in host cells but does not replicate or cause disease for a long time, sometimes for many years. Latent viral infections may be transmissible during the asymptomatic period, facilitating person-to-person spread. Sometimes a trigger (particularly immunosuppression) causes reactivation. Common viruses that remain latent include herpesviruses, HIV, and papovaviruses. Chronic viral infections are characterized by continuous, prolonged viral shedding; examples are congenital infection with rubella virus or with cytomegalovirus and persistent hepatitis B or C. HIV can cause both latent and chronic infections.
Some disorders are caused by viral reactivation in the CNS after a very long latency period. These diseases include progressive multifocal leukoencephalopathy (due to the JC virus, a polyomavirus), subacute sclerosing panencephalitis (due to measles virus), and progressive rubella panencephalitis (due to rubella virus). Variant Creutzfeldt-Jakob disease and bovine spongiform encephalopathy were formerly termed slow viral diseases because they have lengthy incubations (years), but they are now known to be caused by prions; prions are proteinaceous disease-causing agents that are not bacterial, fungal, or viral and that contain no genetic material (see Overview of Prion Diseases).
Several hundred different viruses infect humans. Viruses that infect primarily humans often spread via respiratory and enteric excretions. Some are transmitted sexually and through transfer of blood (eg, via transfusion, mucosal contact, or puncture by a contaminated needle) or through transplantation of tissue. Many viruses are transmitted via rodent or arthropod vectors, and bats have recently been identified as hosts for almost all mammalian viruses, including some responsible for certain serious human infections (eg, severe acute respiratory syndrome [SARS]). Viruses exist worldwide, but their spread is limited by inborn resistance, prior immunizing infections or vaccines, sanitary and other public health control measures, and prophylactic antiviral drugs.
Zoonotic viruses (see Arboviridae, Arenaviridae, and Filoviridae) pursue their biologic cycles chiefly in animals; humans are secondary or accidental hosts. These viruses are limited to areas and environments able to support their nonhuman natural cycles of infection (vertebrates, arthropods, or both).
Some viruses are oncogenic and predispose to certain cancers:
Papillomavirus: Cervical, penile, vaginal, anal, oropharyngeal, and esophageal carcinomas
Human T-lymphotropic virus 1: Certain types of human leukemia and lymphoma
Epstein-Barr virus: Nasopharyngeal carcinoma, Burkitt lymphoma, Hodgkin lymphoma, and lymphomas in immunosuppressed organ transplant recipients
Hepatitis B and C viruses: Hepatocellular carcinoma
Human herpesvirus 8: Kaposi sarcoma, primary effusion lymphomas, and multicentric Castleman disease (a lymphoproliferative disorder)
Some viral disorders can be diagnosed clinically (eg, by well-known viral syndromes such as measles, rubella, roseola infantum, erythema infectiosum, and chickenpox) or epidemiologically (eg, during epidemic outbreaks such as influenza, norovirus infection, and mumps). Definitive laboratory diagnosis is necessary mainly when specific treatment may be helpful or when the agent may be a public health threat (eg, HIV). Typical hospital laboratories can test for some viruses, but for less common disorders (eg, rabies, Eastern equine encephalitis, human parvovirus B19), specimens must be sent to state health laboratories or the Centers for Disease Control and Prevention.
Serologic examination during acute and convalescent stages is sensitive and specific, but slow; more rapid diagnosis can sometimes be made using culture, PCR, or viral antigen tests. Histopathology with electron (not light) microscopy can sometimes help. For specific diagnostic procedures, see Laboratory Diagnosis of Infectious Disease.
Viral genomes are small; the genome of RNA viruses ranges from 3.5 kilobases (some retroviruses) to 27 kilobases (some reoviruses), and the genome of DNA viruses ranges from 5 kilobases (some parvoviruses) to 280 kilobases (some poxviruses). This manageable size together with the current advances in nucleotide sequencing technology means that partial and whole virus genome sequencing will become an essential component in epidemiologic investigations of disease outbreaks.
Progress in the use of antiviral drugs is occurring rapidly. Antiviral chemotherapy can be directed at various phases of viral replication: It can interfere with viral particle attachment to host cell membranes or uncoating of viral nucleic acids, inhibit a cellular receptor or factor required for viral replication, or block specific virus-coded enzymes and proteins that are produced in the host cells and that are essential for viral replication but not for normal host cell metabolism.
Antiviral drugs are most often used therapeutically or prophylactically against herpesviruses (including cytomegalovirus—see Herpesviruses), respiratory viruses (see Respiratory Viruses), and HIV (see Human Immunodeficiency Virus (HIV)). However, some drugs are effective against many different kinds of viruses. Some drugs active against HIV are used for other viral infections such as hepatitis B.
Interferons are compounds released from infected host cells in response to viral or other foreign antigens. There are many different interferons, which have numerous effects such as blocking translation and transcription of viral RNA and stopping viral replication without disturbing normal host cell function. Interferons are sometimes given attached to polyethylene glycol (pegylated formulations), allowing slow, sustained release of the interferon.
Viral disorders sometimes treated with interferon therapy include
Adverse effects of interferons include fever, chills, weakness, and myalgia, typically starting 7 to 12 h after the first injection and lasting up to 12 h. Depression, hepatitis, and, when high doses are used, bone marrow suppression are also possible.
Vaccines (see Overview of Immunization) work by stimulating immunity. Viral vaccines in general use include hepatitis A, hepatitis B, human papillomavirus, influenza, Japanese encephalitis, measles, mumps, poliomyelitis, rabies, rotavirus, rubella, tick-borne encephalitis, varicella, and yellow fever. Adenovirus and smallpox vaccines are available but used only in high-risk groups (eg, military recruits).
Viral diseases can be eradicated by good vaccines. Smallpox was eradicated in 1978, and the cattle plague rinderpest (caused by a virus closely related to human measles virus) was eradicated in 2011. Poliomyelitis has been eradicated from all but a few countries where logistics and religious sentiment continue to impede vaccination. Measles has been eradicated from some parts of the world, notably the Americas, but because measles is highly contagious and vaccination coverage is incomplete even in regions where it is considered eradicated, final eradication is not imminent. The prospects for eradication of other more intractable virus infections (such as HIV) are presently uncertain.
Immune globulins (see Passive Immunization) are available for passive immune prophylaxis in limited situations. They can be used preexposure (eg, for hepatitis A), postexposure (eg, for rabies or hepatitis), and for treating disease (eg, eczema vaccinatum).
Many viral infections can be prevented by commonsense protective measures (which vary depending on the transmission mode of a given agent). Important measures include hand washing, appropriate food preparation and water treatment, avoidance of contact with sick people, and safe-sex practices. For infections with an insect vector (eg, mosquitoes, ticks), avoiding the vector is important.
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