HIV type 1 variants transmitted to women in Kenya require the CCR5 coreceptor for entry, regardless of the genetic complexity of the infecting virus.
Although nearly half of the HIV-1-infected adults in the world are women, little is known about the virologic determinants of transmission to women. Studies suggest that women are frequently infected with multiple HIV-1 genotypes, whereas men are infected with a single genotype. In the current study, we assessed whether the diverse HIV-1 genomes present at the time of infection in women encode viruses that have diverse coreceptor specificities. For this purpose, we defined the coreceptor requirements of viruses found in recently infected Kenyan women, three of whom had multiple viral genotypes and the remaining two of whom had a single genotype. Full-length envelope clones were amplified directly from blood and the dominant genotypes were identified. Envelope clones derived from all five women were able to pseudotype infectious particles competent to infect cells expressing CCR5, but not cells expressing only CXCR4. Thus, regardless of viral complexity at the time of infection, the viruses present at early stages of HIV-1 infection in women use CCR5, suggesting that cells expressing CCR5 are important targets for heterosexual HIV-1 transmission to women.
Long
E Michelle
EM
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Rainwater
Stephanie M J
SM
Lavreys
Ludo
L
Mandaliya
Kishorchandra
K
Overbaugh
Julie
J
D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D005816:Genetic Complementation Test; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007630:Kenya; D008561:Membrane Fusion; D010802:Phylogeny; D015531:Radioimmunoprecipitation Assay; D019713:Receptors, CCR5 / Q000502:physiology*
D017931:DNA Primers; D019713:Receptors, CCR5