Efficient repeated low-dose intravaginal infection with X4 and R5 SHIVs in rhesus macaque: implications for HIV-1 transmission in humans.
We examined the effect of inoculum dose on SHIV transmission and infection. We found that repeated low-dose intravaginal exposure with either R5-SHIV(SF162P3) or X4-SHIV(SF33A) results in infections that are blunted and rapidly controlled. Interestingly, although the transmission rate after all repeated exposures is comparable for the two viruses, the probability of low-dose vaginal transmission is greater for the X4 than R5 virus. Furthermore, X4-SHIV(SF33A) replication predominates in low-dose dually-exposed macaques, suggesting that it is better at establishing a systemic infection following transmission. However, X4-SHIV(SF33A) advantage in transmission and infection is not observed in macaques inoculated intravenously with low-dose mixed inoculum. The finding that although matched in tissue culture infectious dose, the X4 inoculum is more complex leads us to hypothesize that the greater genetic heterogeneity of the X4 virus population may have rendered it less susceptible to the severe bottleneck effects imposed by IVAG inoculation with small doses, allowing for greater probability of transmission and establishment of a generalized infection. These data have implications for HIV-1 transmission and infection in humans.
Tsai
Lily
L
Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Ave, 7th Floor, New York, NY 10016, USA.
Trunova
Nataliya
N
Gettie
Agegnehu
A
Mohri
Hiroshi
H
Bohm
Rudolf
R
Saifuddin
Mohammed
M
Cheng-Mayer
Cecilia
C
D000818:Animals; D018791:CD4 Lymphocyte Count; D004195:Disease Models, Animal; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D015658:HIV Infections / Q000635:transmission; D015497:HIV-1 / Q000254:growth & development; D006801:Humans; D008253:Macaca mulatta; D009092:Mucous Membrane / Q000821:virology; D012367:RNA, Viral / Q000097:blood; D016097:Simian Acquired Immunodeficiency Syndrome / Q000635:transmission*; D015302:Simian Immunodeficiency Virus / Q000254:growth & development*; D014621:Vagina / Q000821:virology*; D019562:Viral Load; D014766:Viremia; D014779:Virus Replication
D012367:RNA, Viral