Conserved CXCR4 usage and enhanced replicative capacity of HIV-2/287, an isolate highly pathogenic in Macaca nemestrina.
OBJECTIVE
To investigate viral properties that contribute to the pathogenic potential of HIV-2 in macaques.


METHODS
We compared HIV-2/287, a virus highly pathogenic in Macaca nemestrina, with its non-pathogenic progenitor HIV-2 EHO, for coreceptor usage and ability to infect human and macaque peripheral blood mononuclear cells (PBMC).


METHODS
Coreceptor usage was determined in GHOST cells expressing known coreceptors, and in PBMC with coreceptor-specific inhibitors. Infectivity in PBMC was determined by virus titration and p27 antigen production. Early and late products of reverse transcription were measured by PCR with primers specific for the long terminal repeat (LTR), or the gag region, respectively.


RESULTS
Both viruses preferentially infect HOS-CD4 cells expressing CXCR4. Inhibition by CXCR4-specific peptide TW70 and monoclonal antibody 12G5 indicated that both viruses use predominantly CXCR4 to infect macaque and human PBMC. HIV-2/287 showed greater infectivity than HIV-2 EHO in macaque cells, but the situation was reversed in human cells. Kinetic analysis of reverse transcription products revealed no restriction in reverse transcription following HIV-2 EHO infection of macaque PBMC. However, comparison of the level of newly initiated HIV-2 EHO DNA in macaque and human PBMC indicated that there is an early restriction, prior to the initiation of reverse transcription.


CONCLUSIONS
Results indicate that the adaptation of HIV-2 EHO in M. nemestrina to a highly pathogenic virus HIV-2/287 is not correlated with a shift in or an expansion of coreceptor usage, but with the acquisition of an ability to overcome restrictions for growth in macaque PBMC.
Rey-Cuille
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MA
Regional Primate Research Center, University of Washington, Seattle, Washington 98121, USA.
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D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D004195:Disease Models, Animal; D015658:HIV Infections / Q000821:virology*; D015498:HIV-2 / Q000472:pathogenicity* / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008254:Macaca nemestrina / Q000821:virology; D019718:Receptors, CXCR4 / Q000378:metabolism*; D014158:Transcription, Genetic; D014779:Virus Replication
D015704:CD4 Antigens; D019718:Receptors, CXCR4