Adaptation of the human immunodeficiency virus type 1 envelope glycoproteins to new world monkey receptors.
Human immunodeficiency virus type 1 (HIV-1) infection encounters an early block in the cells of New World monkeys because the CD4 receptor does not efficiently support HIV-1 entry. We adapted HIV-1(NL4-3) and HIV-1(KB9), two HIV-1 variants with different envelope glycoproteins, to replicate efficiently in cells expressing the CD4 and CXCR4 proteins of the common marmoset, a New World monkey. The HIV-1(NL4-3) adaptation involves three gp120 changes that result in a specific increase in affinity for the marmoset CD4 glycoprotein. The already high affinity of the HIV-1(KB9) envelope glycoproteins for marmoset CD4 did not significantly change as a result of the adaptation. Instead, changes in the gp120 variable loops and gp41 ectodomain resulted in improved replication in cells expressing the marmoset receptors. HIV-1(KB9) became relatively sensitive to neutralization by soluble CD4 and antibodies as a result of the adaptation. These results demonstrate the distinct mechanistic pathways by which the HIV-1 envelope glycoproteins can adapt to less-than-optimal CD4 molecules and provide HIV-1 variants that can overcome some of the early blocks in New World monkey cells.
Pacheco
Beatriz
B
Dana-Farber Cancer Institute, 44 Binney Street, JFB 824, Boston, MA 02115, USA.
Basmaciogullari
Stephane
S
Labonte
Jason A
JA
Xiang
Shi-Hua
SH
Sodroski
Joseph
J
D000220:Adaptation, Biological; D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D002144:Callithrix; D002460:Cell Line; D015699:HIV Envelope Protein gp120 / Q000235:genetics* / Q000502:physiology; D015700:HIV Envelope Protein gp41 / Q000235:genetics* / Q000502:physiology; D015497:HIV-1 / Q000235:genetics* / Q000254:growth & development*; D006801:Humans; D051078:Platyrrhini / Q000821:virology*; D011991:Receptors, Virus / Q000378:metabolism
D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D011991:Receptors, Virus; C514793:gp120 protein, Human immunodeficiency virus 1; C514787:gp41 protein, Human immunodeficiency virus 1