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Coreceptor switch in R5-tropic simian/human immunodeficiency virus-infected macaques.
- Source :
-
Journal of virology [J Virol] 2007 Aug; Vol. 81 (16), pp. 8621-33. Date of Electronic Publication: 2007 May 30. - Publication Year :
- 2007
-
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.
- Subjects :
- Amino Acid Sequence
Amino Acid Substitution
Animals
Antibodies, Viral blood
Disease Models, Animal
HIV isolation & purification
HIV physiology
Macaca mulatta
Membrane Glycoproteins chemistry
Membrane Glycoproteins genetics
Membrane Glycoproteins metabolism
Molecular Sequence Data
Phylogeny
Protein Structure, Secondary
Simian Immunodeficiency Virus isolation & purification
Simian Immunodeficiency Virus physiology
Viral Envelope Proteins chemistry
Viral Envelope Proteins metabolism
Virus Replication
Acquired Immunodeficiency Syndrome virology
Evolution, Molecular
HIV genetics
HIV Infections virology
Receptors, CCR5 physiology
Receptors, CXCR4 physiology
Simian Immunodeficiency Virus genetics
Viral Envelope Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0022-538X
- Volume :
- 81
- Issue :
- 16
- Database :
- MEDLINE
- Journal :
- Journal of virology
- Publication Type :
- Academic Journal
- Accession number :
- 17537860
- Full Text :
- https://doi.org/10.1128/JVI.00759-07