Blockade of HIV-1 infection of New World monkey cells occurs primarily at the stage of virus entry.
HIV-1 naturally infects chimpanzees and humans, but does not infect Old World monkeys because of replication blocks that occur after virus entry into the cell. To understand the species-specific restrictions operating on HIV-1 infection, the ability of HIV-1 to infect the cells of New World monkeys was examined. Primary cells derived from common marmosets and squirrel monkeys support every phase of HIV-1 replication with the exception of virus entry. Efficient HIV-1 entry typically requires binding of the viral envelope glycoproteins and host cell receptors, CD4 and either CCR5 or CXCR4 chemokine receptors. HIV-1 did not detectably bind or utilize squirrel monkey CD4 for entry, and marmoset CD4 was also very inefficient compared with human CD4. A marmoset CD4 variant, in which residues 48 and 59 were altered to the amino acids found in human CD4, supported HIV-1 entry efficiently. The CXCR4 molecules of both marmosets and squirrel monkeys supported HIV-1 infection, but the CCR5 proteins of both species were only marginally functional. These results demonstrate that the CD4 and CCR5 proteins of New World monkeys represent the major restriction against HIV-1 replication in these primates. Directed adaptation of the HIV-1 envelope glycoproteins to common marmoset receptors might allow the development of New World monkey models of HIV-1 infection.
LaBonte
Jason A
JA
Department of Cancer Immunology & AIDS, JFB 824, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.
Babcock
Gregory J
GJ
Patel
Trushar
T
Sodroski
Joseph
J
D000595:Amino Acid Sequence; D000818:Animals; D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology*; D002144:Callithrix; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D006801:Humans; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D016296:Mutagenesis; D019713:Receptors, CCR5 / Q000235:genetics / Q000276:immunology*; D019718:Receptors, CXCR4 / Q000235:genetics / Q000276:immunology*; D012453:Saimiri; D017386:Sequence Homology, Amino Acid
D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D019713:Receptors, CCR5; D019718:Receptors, CXCR4