Coreceptor switch in R5-tropic simian/human immunodeficiency virus-infected macaques.
The basis for the switch from CCR5 to CXCR4 coreceptor usage seen in approximately 50% of human immunodeficiency virus type 1 (HIV-1) subtype B-infected individuals as disease advances is not well understood. Among the reasons proposed are target cell limitation and better immune recognition of the CXCR4 (X4)-tropic compared to the CCR5 (R5)-tropic virus. We document here X4 virus emergence in a rhesus macaque (RM) infected with R5-tropic simian/human immunodeficiency virus, demonstrating that coreceptor switch can happen in a nonhuman primate model of HIV/AIDS. The switch to CXCR4 usage in RM requires envelope sequence changes in the V3 loop that are similar to those found in humans, suggesting that the R5-to-X4 evolution pathways in the two hosts overlap. Interestingly, compared to the inoculating R5 virus, the emerging CXCR4-using virus is highly neutralization sensitive. This finding, coupled with the observation of X4 evolution and appearance in an animal with undetectable circulating virus-specific antibody and low cellular immune responses, lends further support to an inhibitory role of antiviral immunity in HIV-1 coreceptor switch.
Ho
Siu-hong
SH
Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Avenue, New York, NY 10016, USA.
Tasca
Silvana
S
Shek
Lili
L
Li
Amy
A
Gettie
Agegnehu
A
Blanchard
James
J
Boden
Daniel
D
Cheng-Mayer
Cecilia
C
D000163:Acquired Immunodeficiency Syndrome / Q000821:virology*; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D004195:Disease Models, Animal; D019143:Evolution, Molecular; D006678:HIV / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D015658:HIV Infections / Q000821:virology*; D008253:Macaca mulatta; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D010802:Phylogeny; D017433:Protein Structure, Secondary; D019713:Receptors, CCR5 / Q000502:physiology*; D019718:Receptors, CXCR4 / Q000502:physiology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication
D000914:Antibodies, Viral; D008562:Membrane Glycoproteins; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D014759:Viral Envelope Proteins; C069623:gp120 protein, Simian immunodeficiency virus