About: Selective use of primate CD4 receptors by HIV-1

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An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Selective use of primate CD4 receptors by HIV-1
Creator	Dirasanthaid, Obaiah Feldman, Emily Meyerson, Nicholas Sawyerid, Sara Warrenid, Cody Wilkersonid, Gregory
Source	PMC
abstract	Individuals chronically infected with HIV-1 harbor complex viral populations within their bloodstreams. Recently, it has come to light that when these people infect others, the new infection is typically established by only one or a small number of virions from within this complex viral swarm. An important goal is to characterize the biological properties of HIV-1 virions that seed and exist early in new human infections because these are potentially the only viruses against which a prophylactic HIV-1 vaccine would need to elicit protection. This includes understanding how the Envelope (Env) protein of these virions interacts with the T-cell receptor CD4, which supports attachment and entry of HIV-1 into target cells. We examined early HIV-1 isolates for their ability to infect cells via the CD4 receptor of 15 different primate species. Primates were the original source of HIV-1 and now serve as valuable animal models for studying HIV-1. We find that most primary isolates of HIV-1 from the blood, including early isolates, are highly selective and enter cells through some primate CD4 receptor orthologs but not others. This phenotype is remarkably consistent, regardless of route of transmission, viral subtype, or time of isolation post infection. We show that the weak CD4 binding affinity of blood-derived HIV-1 isolates is what makes them sensitive to the small sequence differences in CD4 from one primate species to the next. To substantiate this, we engineered an early HIV-1 Env to have high, medium, or low binding affinity to CD4, and we show that it loses the ability to enter cells via the CD4 receptor of many primate species as the binding affinity gets weaker. Based on the phenotype of selective use of primate CD4, we find that weak CD4 binding appears to be a nearly universal property of HIV-1 circulating in the bloodstream. Therefore, weak binding to CD4 must be a selected and important property in the biology of HIV-1 in the body. We identify six primate species that encode CD4 receptors that fully support the entry of early HIV-1 isolates despite their low binding affinity for CD4. These findings will help inform long-standing efforts to model HIV-1 transmission and early disease in primates.
has issue date	2019-06-10(xsd:dateTime)
bibo:doi	10.1371/journal.pbio.3000304
bibo:pmid	31181085
has license	cc-by
sha1sum (hex)	0666ca679df1885492aa1420fd995790d363b8a5
schema:url	https://doi.org/10.1371/journal.pbio.3000304
resource representing a document's title	Selective use of primate CD4 receptors by HIV-1
has PubMed Central identifier	PMC6586362
has PubMed identifier	31181085
schema:publication	PLoS Biol
resource representing a document's body	covid:0666ca679df1885492aa1420fd995790d363b8a5#body_text
is schema:about of	named entity 'medium' named entity 'HIV-1' named entity 'enter' named entity 'primate' named entity 'time' named entity 'bloodstream' named entity 'infection' named entity 'CD4 RECEPTORS' named entity 'EXIST' named entity 'NEW INFECTION' named entity 'INFORM' named entity 'BIOLOGY' named entity 'INFECTION' named entity 'RECEPTOR' named entity 'ENTER' named entity 'HAVE' named entity 'ISOLATION' named entity 'UNDERSTANDING' named entity 'NUMBER OF' named entity 'SEED' named entity 'SERVE' named entity 'ENV' named entity 'NEARLY' named entity 'BIOLOGICAL PROPERTIES' named entity 'INFECT' named entity 'FULLY' named entity 'FINDINGS' named entity 'SELECTIVE' named entity 'CONSISTENT' named entity 'HUMAN' named entity 'BASED' named entity 'THESE' named entity 'MEDIUM' named entity 'SEQUENCE' named entity 'PEOPLE' named entity 'HELP' named entity 'INFECTIONS' named entity 'VIRIONS' named entity 'TRANSMISSION' named entity 'EARLY DISEASE' named entity 'ROUTE' named entity 'NEED' named entity 'PHENOTYPE' named entity 'INDIVIDUALS' named entity 'PROTECTION' named entity 'ENCODE' named entity 'PROPERTY' named entity 'WHAT' named entity 'BLOODSTREAM' named entity 'NEW' named entity 'CHRONICALLY' named entity 'ISOLATES' named entity 'PRIMARY' named entity 'BLOOD' named entity 'BODY' named entity 'POPULATIONS' named entity 'BUT' named entity 'USE OF' named entity 'SMALL' named entity 'COME' named entity 'LOW' named entity 'PRIMATE' named entity 'VIRUSES' named entity 'INCLUDING' named entity 'LONG' named entity 'THEIR' named entity 'LIGHT' named entity 'INCLUDES' named entity 'IMPORTANT' named entity 'ENTRY' named entity 'GOAL' named entity 'WEAK' named entity 'SELECTED' named entity 'EARLY' named entity 'HIV-1' named entity 'USE OF'

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