TY - JOUR
T1 - Factors associated with siman immunodeficiency virus transmission in a natural african nonhuman primate host in the wild
AU - Ma, Dongzhu
AU - Jasinska, Anna J.
AU - Feyertag, Felix
AU - Wijewardana, Viskam
AU - Kristoff, Jan
AU - He, Tianyu
AU - Raehtz, Kevin
AU - Schmitt, Christopher A.
AU - Jung, Yoon
AU - Cramer, Jennifer Danzy
AU - Dione, Michel
AU - Antonio, Martin
AU - Tracy, Russell
AU - Turner, Trudy
AU - Robertson, David L.
AU - Pandrea, Ivona
AU - Freimer, Nelson
AU - Apetreia, Cristian
N1 - P01 AI088564, NIAID NIH HHS, United StatesR01 HL117715, NHLBI NIH HHS, United StatesR01 HL117715, NHLBI NIH HHS, United StatesR01 RR025781, NCRR NIH HHS, United StatesR01OD010980, NIH HHS, United StatesR01RR016300, NCRR NIH HHS, United StatesR56 DE023508, NIDCR NIH HHS, United States, Biotechnology and Biological Sciences Research Council, United Kingdom, Medical Research Council, United Kingdom
PY - 2014
Y1 - 2014
N2 - African green monkeys (AGMs) are naturally infected with simian immunodeficiency virus (SIV) at high prevalence levels and do not progress to AIDS. Sexual transmission is the main transmission route in AGM, while mother-to-infant transmission (MTIT) is negligible. We investigated SIV transmission in wild AGMs to assess whether or not high SIV prevalence is due to differences in mucosal permissivity to SIV (i.e., whether the genetic bottleneck of viral transmission reported in humans and macaques is also observed in AGMs in the wild). We tested 121 sabaeus AGMs (Chlorocebus sabaeus) from the Gambia and found that 53 were SIV infected (44%). By combining serology and viral load quantitation, we identified 4 acutely infected AGMs, in which we assessed the diversity of the quasispecies by single-genome amplification (SGA) and documented that a single virus variant established the infections. We thus show that natural SIV transmission in the wild is associated with a genetic bottleneck similar to that described for mucosal human immunodeficiency virus (HIV) transmission in humans. Flow cytometry assessment of the immune cell populations did not identify major differences between infected and uninfected AGM. The expression of the SIV coreceptor CCR5 on CD4+ T cells dramatically increased in adults, being higher in infected than in uninfected infant and juvenile AGMs. Thus, the limited SIV MTIT in natural hosts appears to be due to low target cell availability in newborns and infants, which supports HIV MTIT prevention strategies aimed at limiting the target cells at mucosal sites. Combined, (i) the extremely high prevalence in sexually active AGMs, (ii) the very efficient SIV transmission in the wild, and (iii) the existence of a fraction of multiparous females that remain uninfected in spite of massive exposure to SIV identify wild AGMs as an acceptable model of exposed, uninfected individuals. © 2014, American Society for Microbiology.
AB - African green monkeys (AGMs) are naturally infected with simian immunodeficiency virus (SIV) at high prevalence levels and do not progress to AIDS. Sexual transmission is the main transmission route in AGM, while mother-to-infant transmission (MTIT) is negligible. We investigated SIV transmission in wild AGMs to assess whether or not high SIV prevalence is due to differences in mucosal permissivity to SIV (i.e., whether the genetic bottleneck of viral transmission reported in humans and macaques is also observed in AGMs in the wild). We tested 121 sabaeus AGMs (Chlorocebus sabaeus) from the Gambia and found that 53 were SIV infected (44%). By combining serology and viral load quantitation, we identified 4 acutely infected AGMs, in which we assessed the diversity of the quasispecies by single-genome amplification (SGA) and documented that a single virus variant established the infections. We thus show that natural SIV transmission in the wild is associated with a genetic bottleneck similar to that described for mucosal human immunodeficiency virus (HIV) transmission in humans. Flow cytometry assessment of the immune cell populations did not identify major differences between infected and uninfected AGM. The expression of the SIV coreceptor CCR5 on CD4+ T cells dramatically increased in adults, being higher in infected than in uninfected infant and juvenile AGMs. Thus, the limited SIV MTIT in natural hosts appears to be due to low target cell availability in newborns and infants, which supports HIV MTIT prevention strategies aimed at limiting the target cells at mucosal sites. Combined, (i) the extremely high prevalence in sexually active AGMs, (ii) the very efficient SIV transmission in the wild, and (iii) the existence of a fraction of multiparous females that remain uninfected in spite of massive exposure to SIV identify wild AGMs as an acceptable model of exposed, uninfected individuals. © 2014, American Society for Microbiology.
U2 - 10.1128/JVI.03606-13
DO - 10.1128/JVI.03606-13
M3 - Article
C2 - 24623416
SN - 1098-5514
VL - 88
SP - 5687
EP - 5705
JO - Journal of virology
JF - Journal of virology
IS - 10
ER -
