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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,4,7]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>No host-encoded restriction factor identified thus far inhibits the first step of HIV-1 infection: virus\u2013cell attachment. Here we demonstrate that virion-incorporated host transmembrane proteins PSGL-1 and CD43 inhibit attachment of HIV-1 particles to target cells. This inhibition of virus attachment occurs regardless of molecules mediating virus\u2013cell binding and leads to inhibition of both cell-free infection and bystander cell-mediated transinfection. We also show that coclustering of HIV-1 structural protein Gag with PSGL-1 and subsequent progeny virion release contribute to depletion of PSGL-1 from an infected cell surface. Our study reveals an anti\u2013HIV-1 mechanism in which virion-incorporated host transmembrane proteins block virus attachment. 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