TY - JOUR
T1 - Relative Transmissibility of an R5 Clade C Simian-Human Immunodeficiency Virus Across Different Mucosae in Macaques Parallels the Relative Risks of Sexual HIV-1 Transmission in Humans via Different Routes
AU - Chenine, Agnès L.
AU - Siddappa, Nagadenahalli B.
AU - Kramer, Victor G.
AU - Sciaranghella, Gaia
AU - Rasmussen, Robert A.
AU - Lee, Sandra J.
AU - Santosuosso, Michael
AU - Poznansky, Mark C.
AU - Velu, Vijayakumar
AU - Amara, Rama R.
AU - Souder, Chris
AU - Anderson, Daniel C.
AU - Villinger, François
AU - Else, James G.
AU - Novembre, Francis J.
AU - Strobert, Elizabeth
AU - O'Neil, Shawn P.
AU - Secor, Evan W.
AU - Ruprecht, Ruth M.
N1 - Funding Information:
Financial support: National Institutes of Health (grants P01 AI048240, R01 DE012937, R01 DE016013, R56 AI062515, and base grant RR-00165), providing support to the Yerkes National Primate Research Center. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.
PY - 2010/4/15
Y1 - 2010/4/15
N2 - Background. Worldwide, ∼90% of all human immunodeficiency virus (HIV) transmissions occur mucosally; almost all involve R5 strains. Risks of sexual HIV acquisition are highest for rectal, then vaginal, and finally oral exposures. Methods. Mucosal lacerations may affect the rank order of susceptibility to HIV but cannot be assessed in humans. We measured relative virus transmissibility across intact mucosae in macaques using a single stock of SHIV-1157ipd3N4, a simian-human immunodeficiency virus encoding a primary R5 HIV clade C env (SHIV-C). Results. The penetrability of rhesus macaque mucosae differed significantly, with rectal challenge requiring the least virus, followed by vaginal and then oral routes (P = .031, oral vs vaginal; P< .001 rectal vs vaginal). These findings imply that intrinsic mucosal properties are responsible for the differential mucosal permeability. The latter paralleled the rank order reported for humans, with relative risk estimates within the range of epidemiological human studies. To test whether inflammation facilitates virus transmission-as predicted from human studies-we established a macaque model of localized buccal inflammation. Systemic infection occurred across inflamed but not normal buccal mucosa. Conclusion. Our primate data recapitulate virus transmission risks observed in humans, thus establishing R5 SHIV-1157ipd3N4 in macaques as a robust model system to study cofactors involved in human mucosal HIV transmission and its prevention.
AB - Background. Worldwide, ∼90% of all human immunodeficiency virus (HIV) transmissions occur mucosally; almost all involve R5 strains. Risks of sexual HIV acquisition are highest for rectal, then vaginal, and finally oral exposures. Methods. Mucosal lacerations may affect the rank order of susceptibility to HIV but cannot be assessed in humans. We measured relative virus transmissibility across intact mucosae in macaques using a single stock of SHIV-1157ipd3N4, a simian-human immunodeficiency virus encoding a primary R5 HIV clade C env (SHIV-C). Results. The penetrability of rhesus macaque mucosae differed significantly, with rectal challenge requiring the least virus, followed by vaginal and then oral routes (P = .031, oral vs vaginal; P< .001 rectal vs vaginal). These findings imply that intrinsic mucosal properties are responsible for the differential mucosal permeability. The latter paralleled the rank order reported for humans, with relative risk estimates within the range of epidemiological human studies. To test whether inflammation facilitates virus transmission-as predicted from human studies-we established a macaque model of localized buccal inflammation. Systemic infection occurred across inflamed but not normal buccal mucosa. Conclusion. Our primate data recapitulate virus transmission risks observed in humans, thus establishing R5 SHIV-1157ipd3N4 in macaques as a robust model system to study cofactors involved in human mucosal HIV transmission and its prevention.
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U2 - 10.1086/651274
DO - 10.1086/651274
M3 - Article
C2 - 20214475
AN - SCOPUS:77950196210
VL - 201
SP - 1155
EP - 1163
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
SN - 0022-1899
IS - 8
ER -