What Are Retroviruses And Their Features
Retroviridae is a family of viruses composed of seven generae which are commonly and collectively referred to as retroviruses. The first retroviruses were initially discovered and characterized as agents that cause various cancers in chickens (Ellerman & Bang 1908, Rous 1911). Much later, in 1970, two independent discoveries of a defining component of retroviruses were made– reverse transcriptase, an RNA dependent DNA polymerase (Baltimore 1970, Temin & Mizutani 1970). The presence of reverse transcriptase would then be used as a preliminary assay towards demonstrating the existence of human retroviruses, beginning with the Human T-cell leukemia virus (HTLV-1) (Poiesz et al. 1980, Hinuma et al. 1982), and later followed by others, including HTLV-2 and HIV.
Generally, retroviruses have a single stranded positive sense RNA genome that is: approximately 7 to 11 kilobases in length, monopartite, 5’ capped with a 3’ poly-A tail and long terminal repeats, and dimeric/diploid. Their replication cycle begins with viral attachment at the cell membrane via the SU glycoprotein (also named gp120). Attached viruses can then undergo fusion with the help of the TM glycoprotein. After uncoating, the viral genome can undergo reverse transcription wherein reverse transcriptase uses the virus’ single stranded RNA genome as a template to make double stranded DNA (dsDNA). This dsDNA is then transported to and enters the nucleus where it can be incorporated into the host genome with the help of viral integrase. The host cell’s RNA polymerase II then transcribes viral RNAs. These RNAs can then be exported from the nucleus, leading to unspliced RNAs undergoing translation to produce env, gag, and gag-pol polyproteins. New virions are then able to assemble at the host cell membrane, including packaging of the viral RNA genome. Newly formed virions are then released from the cell via budding.
Post-release, new retroviral virions mature as viral protease cleaves viral polyproteins (Pommier et al. 2005). Two types of retrovirus have the biggest impact on human health– Human T-cell leukemia virus (HLTV) and Human immunodeficiency virus (HIV). It was recently estimated that 36.9 million people were living worldwide with AIDS (acquired immunodeficiency syndrome) (unicef, 2017) and that from 2000-2015, $562.6 billion was spent combatting HIV/AIDS (Global Burden of Disease Health Financing Collaborator Network, 2018). Both HTLV and HIV can lead to asymptomatic infections as well as more serious conditions from chronic infection. HTLV can produce Adult T-cell leukemia (ATL) as well as Tropical spastic paraparesis, while HIV can lead to AIDS– a progressive immune deficiency that can ultimately result in recurring opportunistic infections and neurological abnormalities.
HIV can also acutely lead to more common symptoms including: fever, sweats, muscle and joint soreness, swollen lymph nodes, nausea, vomiting, diarrhea, headaches, and rash. HIV and HTLV are both transmitted from certain bodily fluids (blood, semen, vaginal fluids, breast milk) directly contacting mucous membranes or damaged tissue, or entering the blood stream. Thus, transmission can occur during breast feeding (unless combined with antiviral treatment), direct blood contact (such as a blood transfusion), sexual intercourse, and/or from use of contaminated needles/syringes (Cloyd 1996). There are three main types of diagnostic tests for retroviruses (including HTLV and HIV): 1) nucleic acid tests (NATs) that detect viral nucleic acids, 2) antigen/antibody tests that detect viral antigens (in the case of HIV, primarily p24 is screened for), and 3) antibody tests that detect antibodies produced against viral proteins (CDC). Which test is most appropriate depends on considerations including the cost of the tests, how long a person has been infected, and how rapidly they need the results.
