Envelope glycoprotein determinants of increased entry in a pathogenic simian-human immunodeficiency virus (SHIV-HXBc2P 3.2) passaged in monkeys.
Passage of a nonpathogenic simian-human immunodeficiency virus (SHIV-HXBc2) in monkeys resulted in changes in the viral envelope glycoproteins that are responsible for a dramatic increase in replication and pathogenicity in vivo. Here, we show that the envelope glycoproteins of the pathogenic SHIV-HXBc2P 3.2 mediate virus entry into rhesus monkey peripheral blood mononuclear cells (PBMC) more efficiently than the parental SHIV-HXBc2 envelope glycoproteins, and study the basis for this increase. Both parental and pathogenic SHIVs exclusively use CXCR4 as a coreceptor. The determinants of the increased entry associated with the SHIV-HXBc2P 3.2 envelope glycoproteins are located in both the gp120 and gp41 subunits. Changes in the gp120 V3 variable loop specify a decreased sensitivity to SDF-1, consistent with an increase in the affinity of the HXBc2P 3.2 gp120 glycoprotein for CXCR4. Thus, multiple changes in the gp120 variable loops and the gp41 ectodomain of a pathogenic SHIV cooperate to allow enhanced replicative capacity, which in part results from increased chemokine receptor binding.
Si
Zhihai
Z
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Pathology, Division of AIDS, Harvard Medical School, Boston, Massachusetts 02115, USA.
Gorry
Paul
P
Babcock
Greg
G
Owens
Christopher M
CM
Cayabyab
Mark
M
Phan
Ngoc
N
Sodroski
Joseph
J
D000818:Animals; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000502:physiology; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000502:physiology; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000821:virology; D008253:Macaca mulatta; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology; D019718:Receptors, CXCR4 / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000502:physiology; D011995:Recombination, Genetic; D012191:Retroviridae Proteins / Q000235:genetics / Q000502:physiology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000502:physiology*; D014774:Virulence; D014779:Virus Replication
D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D008562:Membrane Glycoproteins; D019718:Receptors, CXCR4; D011993:Recombinant Fusion Proteins; D012191:Retroviridae Proteins; C082614:SIV envelope protein gp41; D014759:Viral Envelope Proteins; C069623:gp120 protein, Simian immunodeficiency virus