Retroviridae

• TRANSMISSION ROUTE: Direct contact

Definition

The Retroviridae is a family of latent and pathogenic viruses with a positive-sense, single-stranded RNA (ribonucleic acid) genome for replication. Virions contain reverse transcriptase (RT) enzymeswithin a spherical capsid. The viruses infect vertebrate host cells by incorporating themselves into the host DNA (deoxyribonucleic acid).

Natural Habitat and Features

Retroviruses, like traditional viruses, require a host to reproduce; retroviruses only infect vertebrate hosts and use the host DNA instead of messenger RNA to replicate. A particular feature of the retrovirus is that its viral RNA genome is integrated as proviral DNA into the host DNA and is passed to progeny of the host, endogenously. A minimum of nine endogenous retroviruses are present in vertebrate genomes, accounting for approximately 1 percent of the human genome, and they appear latent, with no effect on the hosts. Exogenous retroviruses, which are passed among vertebrates through blood and bodily secretions, can be more pathogenic.

All seven genera of the two subfamilies of retroviruses share the same mode of replication and basic virion structure, and they spread through host cells rapidly. Retroviruses consist of a lipid envelope that surrounds a spherical and electron-dense protein core, or capsid. Within the 100-nanometer-diameter capsid are two copies of a 10,000-base pair, single-stranded RNA genome that contains repeats of essential gag- pol- env genes in the long terminal ends. Enzymes for host DNA incorporation and genome replication (integrase and RT) are found in the core as well. Pathogenic retroviruses also contain more complex genes (such as tat and rev).

Retrovirus particles infect host cells rapidly and efficiently by attaching to and entering the host cell and converting single-stranded RNA into double-stranded DNA (proviral DNA) to build a double-stranded DNA provirus that inserts itself into the host DNA. Immature viral particles are then released from the infected host cell to spread throughout the body. This viral framework persists for the entire lifetime of the host. Retroviruses can evolve rapidly and repeatedly on the basis of selective needs, resulting from immune attacks or administered drugs. The individual adaptive mutations complicate treatment greatly, because each infected host’s virus can vary according to differing antiviral attacks.

Although retroviruses were first discovered in 1908 by Vilhem Ellermann and Oluf Bang, the RT enzyme used for the replication process was not discovered until 1970. Human T-lymphocyte virus (HTLV) was the first pathogenic retrovirus isolated, in 1980, closely followed in 1984 by human immunodeficiency virus (HIV).

Pathogenicity and Clinical Significance

Outcomes of pathogenic retroviral infections are host specific and may be neurologic, immunodeficient, or wasting. Namely, HIV leads to acquired immunodeficiency syndrome (AIDS) and HTLV causes adult T-cell leukemia.

HIV is transmitted through sexual secretions, shared needles from injection-drug use, blood, placental fluids, mucosal fluids, and breast milk. Symptoms are initially similar to those of influenza, with body aches and fever. Gradually, symptoms disappear as the immune system attacks the virus, despite viral integration into the host; as the virus begins to overwhelm the host’s cells, immune deterioration begins. HIV is monitored by measuring the levels of host cells in the plasma (the viral load) infected by the virus and by measuring the immune system cell count (CD4 count).

Because retroviruses can change the host genome, they also can develop oncogenes in the body. Infection with HTLV-1 leads to the formation of tumors that can lead to adult T-cell leukemia. HTLV is spread through perinatal and sexual transmission or through contact with infected blood products. HTLV leukemia is an aggressive disease that has a mortality of approximately one year. In equatorial areas of the world, infection with HTLV-1 may cause tropical spastic paraparesis, with symptoms of neurologic deficiency.

Drug Susceptibility

HIV is the primary pathogenic retrovirus against which drug treatments have been developed. Since the development of the first antiretroviral (ARV) agent, the nucleoside reverse transcriptase inhibitor zidovudine, in 1987, five classes of ARV drugs have been developed against HIV. All ARV classes attack HIV at different stages of replication, cell entry, or DNA integration to slow the viral assault.

Nucleoside reverse transcriptase inhibitors replace normal genome building blocks to stop virus reproduction, and non-nucleoside reverse transcriptase inhibitors disable the RT enzyme for the same effect. Protease inhibitors prevent action of a replicating enzyme, fusion and entry inhibitors prevent steps needed for entry into host cells, and integrase inhibitors disable the enzyme used for DNA incorporation.

ARV drug treatments are introduced as highly active ARV therapy (HAART) regimens for maximum antiviral attack. The particular drugs used vary around a standard, recommended regimen; medications are added, removed, or replaced as necessary when resistance builds to a certain drug or entire mechanistic class. Atripla, a combination pill that contains efavirenz (an NNRTI), emtricitabine (an NRTI), and tenofovir (another NRTI), is an example of an initial HAART regimen for a person newly diagnosed with HIV.

Because retroviral genomes have the ability to change and adapt to outside pressures rapidly and efficiently, drug susceptibility varies by viral strain and by particular infected host, and it depends on immune system attacks and on treatments administered to the host. Extensive genotypic and phenotypic susceptibility testing may be performed in persons with HIV, and can be analyzed by infectious disease experts to identify specific drug agents or classes that retain effectiveness and suppress HIV replication.

More often, the infected person’s viral load is measured every six to eight weeks and compared with earlier measurements to manage a treatment regimen. If HAART is effective, viral load will be reduced, reflecting lower levels of virus in the blood. If, after twenty days on a regimen, viral load is not lowered to undetectable levels, the regimen is considered ineffective and can lead to virologic failure without a change of therapy.

In addition to researching expanded drug options within each ARV class, HIV researchers are studying methods to prevent initial retrovirus infection. These experimental methods include using microbicidal agents as mucosal barriers in sexual contact and using a vaccine against HIV.

Bibliography

Boucher, Charles A. B. “Retroviruses and Retroviral Infections.” In Cohen and Powderly Infectious Diseases, edited by Jonathan Cohen, Steven M. Opal, and William G. Powderly. 3d ed. Philadelphia: Mosby/Elsevier, 2010.

“A Brief Chronicle of Retrovirology.” In Retroviruses, edited by J. M. Coffin, S. H. Hughes, and H. E. Varmus. Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory Press, 2002 Also available at http://www.ncbi.nlm.nih.gov/books/nbk19403.

Kurth, R., and N. Bannert, eds. Retroviruses: Molecular Biology, Genomics, and Pathogenesis. Norwich, England: Caister Academic Press, 2010.

Luzuriaga, Katherine, and John L. Sullivan. “Introduction to Retroviridae.” In Principles and Practice of Pediatric Infectious Diseases, edited by Sarah S. Long, Larry K. Pickering, and Charles G. Prober. 3d ed. Philadelphia: Churchill Livingstone/Elsevier, 2008.

"Retroviruses That May Cause Human Illness." Minnesota Department of Health, 19 Oct. 2022, www.health.state.mn.us/diseases/retrovirus/index.html. Accessed 4 Feb. 2025.