Species-specific tropism determinants in the human immunodeficiency virus type 1 capsid

Retroviral tropism is determined in part by cellular restriction factors that block infection by targeting the incoming viral capsid. Indeed, human immunodeficiency virus type 1 (HIV-1) infection of many nonhuman primate cells is inhibited by one such factor, termed Lv1. In contrast, a restriction f...

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Published in:Journal of virology Vol. 78; no. 11; p. 6005
Main Authors: Hatziioannou, Theodora, Cowan, Simone, Von Schwedler, Uta K, Sundquist, Wesley I, Bieniasz, Paul D
Format: Journal Article
Language:English
Published: United States 01.06.2004
Subjects:
Amino Acid Sequence
Animals
Capsid - chemistry
Cell Line
DNA-(Apurinic or Apyrimidinic Site) Lyase - physiology
HIV-1 - chemistry
Humans
Molecular Sequence Data
Species Specificity
Virion - chemistry
ISSN:0022-538X
Online Access:Get more information
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Summary:Retroviral tropism is determined in part by cellular restriction factors that block infection by targeting the incoming viral capsid. Indeed, human immunodeficiency virus type 1 (HIV-1) infection of many nonhuman primate cells is inhibited by one such factor, termed Lv1. In contrast, a restriction factor in humans, termed Ref1, does not inhibit HIV-1 infection unless nonnatural mutations are introduced into the HIV-1 capsid protein (CA). Here, we examined the infectivity of a panel of mutant HIV-1 strains carrying substitutions in the N-terminal CA domain in cells that exhibit restriction attributable to Lv1 or Ref1. Manipulation of HIV-1 CA could alter HIV-1 tropism, and several mutations were identified that increased or decreased HIV-1 infectivity in a target-cell-specific manner. Many residues that affected HIV-1 tropism were located in the three variable loops that lie on the outer surface of the modeled HIV-1 conical capsid. Some tropism determinants, including the CypA binding site, coincided with residues whose mutation conferred on HIV-1 CA the ability to saturate Ref1 in human cells. Notably, a mutation that reverses the infectivity defect in human cells induced by CypA binding site mutation inhibits recognition by Ref1. Overall, these findings demonstrate that exposed variable loops in CA and a partial CypA "coat" can modulate restriction and HIV-1 tropism and suggest a model in which the exposed surface of the incoming retroviral capsid is the target for inhibition by host cell-specific restriction factors.
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ISSN:0022-538X
DOI:10.1128/JVI.78.11.6005-6012.2004