{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:35:55Z","timestamp":1791894955583,"version":"4.3.4"},"reference-count":119,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T00:00:00Z","timestamp":1700092800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01-AI40970, P30-AI050410"],"award-info":[{"award-number":["R01-AI40970, P30-AI050410"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30-CA016086"],"award-info":[{"award-number":["P30-CA016086"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Virol."],"abstract":"<jats:p>\n                    HIV-1 generates remarkable intra- and inter-host viral diversity during infection. In the response to the dynamic selective pressures of the host\u2019s environment, HIV-1 evolves distinct phenotypes\u2014biological features that provide fitness advantages. The transmitted form of HIV-1 has been shown to require a high density of CD4 on the target cell surface (as found on CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells) and typically uses C\u2013C chemokine receptor type 5 (CCR5) as a coreceptor during entry. This phenotype is referred to as R5T cell-tropic (or R5 T-tropic); however, HIV-1 can switch to a secondary coreceptor, C\u2013X\u2013C chemokine receptor type 4 (CXCR4), resulting in a X4T cell-tropic phenotype. Macrophage-tropic (or M-tropic) HIV-1 can evolve to efficiently enter cells expressing low densities of CD4 on their surface (such as macrophages\/microglia). So far only CCR5-using M-tropic viruses have been found. M-tropic HIV-1 is most frequently found within the central nervous system (CNS), and infection of the CNS has been associated with neurologic impairment. It has been shown that interferon-resistant phenotypes have a selective advantage during transmission, but the underlying mechanism of this is still unclear. During untreated infection, HIV-1 evolves under selective pressure from both the humoral\/antibody response and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cell killing. Sufficiently potent antiviral therapy can suppress viral replication, but if the antiviral drugs are not powerful enough to stop replication, then the replicating virus will evolve drug resistance. HIV-1 phenotypes are highly relevant to treatment efforts, clinical outcomes, vaccine studies, and cure strategies. Therefore, it is critical to understand the dynamics of the host environment that drive these phenotypes and how they affect HIV-1 pathogenesis. This review will provide a comprehensive discussion of HIV-1 entry and transmission, and drug-resistant phenotypes. Finally, we will assess the methods used in previous and current research to characterize these phenotypes.\n                  <\/jats:p>","DOI":"10.3389\/fviro.2023.1291996","type":"journal-article","created":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T13:30:18Z","timestamp":1700141418000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Evolution driven by a varying host environment selects for distinct HIV-1 entry phenotypes and other informative variants"],"prefix":"10.3389","volume":"3","author":[{"given":"Shuntai","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Long","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Swanstrom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,11,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1210","article-title":"How retroviruses select their genomes","volume":"3","author":"D\u2019souza","year":"2005","journal-title":"Nat Rev Microbiol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90024-1","article-title":"Retrovirus receptors","volume":"82","author":"Weiss","year":"1995","journal-title":"Cell"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1126\/science.7824947","article-title":"HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy","volume":"267","author":"Coffin","year":"1995","journal-title":"Science"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/35400","article-title":"An African HIV-1 sequence from 1959 and implications for the origin of the epidemic","volume":"391","author":"Zhu","year":"1998","journal-title":"Nature"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1126\/science.288.5472.1789","article-title":"Timing the ancestor of the HIV-1 pandemic strains","volume":"288","author":"Korber","year":"2000","journal-title":"Science"},{"key":"B6","doi-asserted-by":"publisher","first-page":"a006841","DOI":"10.1101\/cshperspect.a006841","article-title":"Origins of HIV and the AIDS pandemic","volume":"1","author":"Sharp","year":"2011","journal-title":"Cold Spring Harb Perspect Med"},{"key":"B7","volume-title":"Global HIV & AIDS statistics\u2014Fact sheet","year":"2021"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-199912240-00007","article-title":"Interruption of reverse transcriptase inhibitors or a switch from reverse transcriptase to protease inhibitors resulted in a fast reappearance of virus strains with a reverse transcriptase inhibitor-sensitive genotype","volume":"13","author":"Verhofstede","year":"1999","journal-title":"AIDS"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200102153440702","article-title":"Virologic and immunologic consequences of discontinuing combination antiretroviral-drug therapy in HIV-infected patients with detectable viremia","volume":"344","author":"Deeks","year":"2001","journal-title":"N Engl J Med"},{"key":"B10","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":"Barr\u00e9-Sinoussi","year":"1983","journal-title":"Science"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/312763a0","article-title":"The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus","volume":"312","author":"Dalgleish","year":"1984","journal-title":"Nature"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(86)90169-8","article-title":"Replicative capacity of human immunodeficiency virus from patients with varying severity of HIV infection","volume":"2","author":"Asj\u00f6","year":"1986","journal-title":"Lancet"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1126\/science.8356453","article-title":"Genotypic and phenotypic characterization of HIV-1 patients with primary infection","volume":"261","author":"Zhu","year":"1993","journal-title":"Science"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.63.5.2118-2125.1989","article-title":"Evidence for a role of virulent human immunodeficiency virus (HIV) variants in the pathogenesis of acquired immunodeficiency syndrome: studies on sequential HIV isolates","volume":"63","author":"Tersmette","year":"1989","journal-title":"J Virol"},{"key":"B15","article-title":"Zidovudine resistance, syncytium-inducing phenotype, and HIV disease progression in a case\u2013control study. 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