Overview of Viruses

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

• Herpesviruses

• Human immunodeficiency virus (HIV)

• Papovaviruses (composed of 2 subgroups: papilloma and polyoma viruses)

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

• Progressive multifocal leukoencephalopathy (due to the JC [John Cunningham] virus, a polyomavirus)

• Subacute sclerosing panencephalitis (due to measles virus)

• Progressive rubella panencephalitis (due to rubella virus)

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:

• Chikungunya

• Dengue

• West Nile

• Zika

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

• Arboviruses such as Zika, West Nile, and dengue

• Lymphocytic choriomeningitis virus [LCMV]

• HIV-1

• Rabies

• Hepatitis B [HBV]

• Herpes simplex virus [HSV]

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.)