Overview of Viruses

ByLaura D Kramer, PhD, Wadsworth Center, New York State Department of Health
Reviewed/Revised Mar 2023
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Viruses are among the smallest microbes, typically ranging from 0.02 to 0.3 micrometer, although several very large viruses up to 1 micrometer in length (megavirus, pandoravirus) have recently been discovered. Viruses depend completely on cells (bacterial, plant, or animal) to reproduce. Some viruses have an outer envelope consisting of protein and lipid, surrounding a protein capsid complex with genomic RNA or DNA and sometimes enzymes needed for the first steps of viral replication.

Classification of viruses is principally according to their genome sequence taking into consideration nature and structure of their genome and their method of replication, but not according to the diseases they cause (see International Committee on Taxonomy of Viruses (ICTV), 2021 release). Thus, there are DNA viruses and RNA viruses; either DNA or RNA viruses may have single or double strands of genetic material. Single-strand RNA viruses are further divided into those with (+) sense and (-) sense RNA. Positive-sense RNA viruses possess a single-stranded RNA genome that can serve as messenger RNA (mRNA) that can be directly translated to produce an amino acid sequence. Negative-sense RNA viruses possess a single-stranded negative-sense genome that first must synthesize a complementary positive-sense antigenome, which is then used to make genomic negative-sense RNA. DNA viruses typically replicate in the host cell nucleus, and RNA viruses typically replicate in the cytoplasm.

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 a germline cell is infected by a retrovirus, 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) (1). 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.

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.

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. Many viral infections are cleared by the immune system, 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

Ebola virus appears to persist in the immunologically privileged sites in the human body (eg, testes, eyes) (2).

Some disorders are caused by viral reactivation in the central nervous system after a very long latency period. These diseases include

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.

Several hundred different viruses infect humans. Viruses that infect primarily humans often spread via respiratory and enteric excretions. Blood that is collected for transfusion is tested for a number of viruses (see table Infectious Disease Transmission Testing). Many viruses are transmitted via rodent or arthropod vectors, and bats have recently been identified as hosts for many mammalian viruses, including some responsible for certain serious human infections (eg, SARS-CoV-2).

Some viruses are transmitted sexually via mucosal contact, such as Zika. Other viruses are transmitted through transfer of blood (eg, through puncture by a contaminated needle, or transfusion), including hepatitis viruses A, B, C, and E, and the following arboviruses:

Cytomegalovirus [CMV] and Epstein–Barr virus are the viruses most predominantly transferred through transplantation of tissue. Other such viruses include

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 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).

Variant Creutzfeldt-Jakob disease and bovine spongiform encephalopathy were initially thought to be caused by a virus and 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 also Types of Viral Disorders.)

Viruses and cancer

Some viruses are oncogenic and predispose to certain cancers:

References

  1. 1. Dupressoir A, Lavialle C, Heidmann T: From ancestral infectious retroviruses to bona fide cellular genes: role of the captured syncytins in placentation. Placenta 33(9):663-671, 2012. doi:10.1016/j.placenta.2012.05.005

  2. 2. Schindell BG, Webb AL, Kindrachuk J: Persistence and sexual transmission of filoviruses. Viruses 10(12):683, 2018. doi: 10.3390/v10120683

Diagnosis of Viral Infections

Some viral disorders can be diagnosed as follows:

Definitive laboratory diagnosis is necessary mainly when specific treatment may be helpful or when the agent may be a public health threat (eg, HIV). Most hospital laboratories can test for many 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 for antibodies during acute and convalescent stages can be sensitive and specific, but slow; with some viruses, especially flaviviruses, cross-reactions confound diagnosis. More rapid diagnosis can sometimes be made using culture, polymerase chain reaction, or viral antigen tests. Histopathology with electron (not light) microscopy can sometimes help. For specific diagnostic procedures, see Laboratory Diagnosis of Infectious Disease.

Treatment of Viral Infections

Antiviral drugs

Progress in the use of antiviral drugs is occurring rapidly. Mechanisms of antiviral drugs can be directed at various phases of viral replication. They 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

  • Block specific virus-encoded 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), respiratory viruses, HIV, chronic hepatitis B, and chronic hepatitis C. However, some drugs are effective against many different kinds of viruses. For example, some drugs active against HIV are used for other viral infections such as hepatitis B.

Antiviral drugs have been developed for treatment of COVID-19, which is caused by SARS-CoV-2.

Interferons

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.

Viral disorders sometimes treated with interferon therapy include

Adverse effects of interferons include fever, chills, weakness, and myalgia, typically starting 7 to 12 hours after the first injection and lasting up to 12 hours. Depression, hepatitis, and, when high doses are used, bone marrow suppression are also possible.

Antibodies

Convalescent serum and monoclonal antibodies (mAbs) can be used to treat some viral infections (eg, Zaire Ebola virus infection, respiratory syncytial virus [RSV], rabies virus).

Prevention of Viral Infections

Vaccines

Vaccines work by stimulating immunity. Viral vaccines in general use include vaccines for

Adenovirus, smallpox, and mpox vaccines, as well as Rift Valley fever and eastern equine encephalitis vaccines are available but used only in high-risk groups (eg, military recruits).

Multiple vaccines for prevention of COVID-19, caused by SARS-CoV-2, have been developed, including mRNA and other types of vaccines.

Viral diseases can be eradicated by effective 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. Extensive vaccination has almost eradicated polio worldwide, but cases still occur in areas with incomplete immunization, such as sub-Saharan Africa and southern Asia. Measles has been almost 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 development of vaccines and eradication of other more intractable virus infections (such as HIV) are presently uncertain.

Immune globulins

Immune globulins are available for passive immune prophylaxis in limited situations. They can be used preexposure (eg, for hepatitis A), postexposure (eg, for rabies, varicella, respiratory syncytial virus, hepatitis), and for treating disease (eg, eczema vaccinatum).

Protective measures

Many viral infections can be prevented by routine 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

  • Safer-sex practices

  • Mask wearing

  • Physical distancing when appropriate (eg, for COVID-19 prevention)

For infections with an insect vector (eg, mosquitoes, ticks), personal protection against vector bites is important, such as repellents, proper clothing.

For infections such as Ebola virus infection, avoiding contact with blood and body fluids (such as urine, feces, saliva, sweat, vomit, breast milk, amniotic fluid, semen, and vaginal fluids) of people who are sick is an important protective measure. Contact with semen from a man who has recovered from Ebola virus infection should be avoided until testing shows that the virus is gone from his semen.

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