Coreceptor switch in R5-tropic simian/human immunodeficiency virus-infected macaques.

Abstract:

: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.

journal_name

J Virol

journal_title

Journal of virology

authors

Ho SH,Tasca S,Shek L,Li A,Gettie A,Blanchard J,Boden D,Cheng-Mayer C

doi

10.1128/JVI.00759-07

subject

Has Abstract

pub_date

2007-08-01 00:00:00

pages

8621-33

issue

16

eissn

0022-538X

issn

1098-5514

pii

JVI.00759-07

journal_volume

81

pub_type

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