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The most recognizable human retrovirus, human immunodeficiency virus type 1 (HIV-1), is the causative agent of the global AIDS epidemic and has been extensively studied. Other human retroviruses, such as human immunodeficiency virus type 2 (HIV-2) and human T-cell leukemia virus type 1 (HTLV-1), have received less attention, and many of the assumptions about the replication and biology of these viruses are based on knowledge of HIV-1. Existing comparative studies on human retroviruses, however, have revealed that key differences between these viruses exist that affect evolution, diversification, and potentially pathogenicity. In this review, we examine current insights on disparities in the replication of pathogenic human retroviruses, with a particular focus on the determinants of structural and genetic diversity amongst HIVs and HTLV.<\/jats:p>","DOI":"10.3389\/fviro.2022.872599","type":"journal-article","created":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T11:16:19Z","timestamp":1654168579000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":30,"title":["Molecular Biology and Diversification of Human Retroviruses"],"prefix":"10.3389","volume":"2","author":[{"given":"Morgan E.","family":"Meissner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathaniel","family":"Talledge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis M.","family":"Mansky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1126\/science.6189183","article-title":"Isolation of a T-Lymphotropic Retrovirus From a Patient at Risk for Acquired Immune Deficiency Syndrome (AIDS)","volume":"220","author":"Barre-Sinoussi","year":"1983","journal-title":"Science"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1126\/science.6601823","article-title":"Isolation of Human T-Cell Leukemia Virus in Acquired Immune Deficiency Syndrome (AIDS)","volume":"220","author":"Gallo","year":"1983","journal-title":"Science"},{"key":"B3","unstructured":"Global HIV & AIDS Statistics \u2014 2019 Fact Sheet2020"},{"key":"B4","unstructured":"HIV Data and Statistics2020"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2016.08.010","article-title":"Hiv-2 Molecular Epidemiology","volume":"46","author":"Visseaux","year":"2016","journal-title":"Infect Genet Evol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a007054","article-title":"The T-Cell Response to HIV","volume":"2","author":"Walker","year":"2012","journal-title":"Cold Spring Harb Perspect Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.50.1.825","article-title":"Immunopathogenesis of HIV Infection","volume":"50","author":"Pantaleo","year":"1996","journal-title":"Annu Rev Microbiol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.puhe.2016.05.004","article-title":"Survival Rate of AIDS Disease and Mortality in HIV-Infected Patients: A Meta-Analysis","volume":"139","author":"Poorolajal","year":"2016","journal-title":"Public Health"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1086\/315010","article-title":"Lower Human Immunodeficiency Virus (HIV) Type 2 Viral Load Reflects the Difference in Pathogenicity of HIV-1 and HIV-2","volume":"180","author":"Popper","year":"1999","journal-title":"J Infect Dis"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.160.21.3286","article-title":"Plasma Viral Load in HIV-1 and HIV-2 Singly and Dually Infected Individuals in Guinea-Bissau, West Africa: Significantly Lower Plasma Virus Set Point in HIV-2 Infection Than in HIV-1 Infection","volume":"160","author":"Andersson","year":"2000","journal-title":"Arch Intern Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(94)90065-5","article-title":"Slower Heterosexual Spread of HIV-2 Than HIV-1","volume":"343","author":"Kanki","year":"1994","journal-title":"Lancet"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1994.03520060062033","article-title":"Prospective Comparison of Mother-to-Child Transmission of HIV-1 and HIV-2 in Abidjan, Ivory Coast","volume":"272","author":"Adjorlolo-Johnson","year":"1994","journal-title":"JAMA"},{"key":"B13","article-title":"Maternal Plasma Viral RNA Levels Determine Marked Differences in Mother-to-Child Transmission Rates of HIV-1 and HIV-2 in The Gambia. 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