Abstract
Despite the fact that approximately half of all HIV patients acquire infection through penile exposure, there have been no recent studies of penile SIV transmission in rhesus macaques and the nature of the virus variants transmitted, target cells, and pathways of virus dissemination to systemic lymphoid tissues are not known. Single genome amplification (SGA) and sequencing of HIV-1 RNA in plasma of acutely infected humans allows the identification and enumeration of transmitted/founder viruses responsible for productive systemic infection. Studies using the SGA strategy have shown that intrarectal and intravaginal SIV transmission to macaques recapitulates key features of human HIV transmission. To date, no studies have used the SGA assay to identify transmitted/founder virus(es) in macaques infected after penile SIV exposure. Here we report that SIV can be transmitted by penile SIV exposure. However, similar exposure to a high-dose inoculum infects only about half the animals, which is about 50% less efficient transmission than occurs after vaginal SIV challenge. In addition, only a single SIV env variant established the systemic infection in all five animals that became infected after penile exposure, a result that is consistent with low incidence and few transmitted HIV variants in heterosexually infected men. Our results suggest that the penile transmission of SIVmac251 in rhesus macaques recapitulates the key features of penile HIV-1 transmission and may provide insight into host or viral factors that permit penile transmission and dissemination. Furthermore, this SIV challenge exposure route will be useful in testing vaccines and other prophylactic approaches.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1259-1269 |
| Number of pages | 11 |
| Journal | AIDS Research and Human Retroviruses |
| Volume | 27 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 1 2011 |
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ASJC Scopus subject areas
- Immunology
- Virology
- Infectious Diseases
Cite this
SIVmac251 Is inefficiently transmitted to rhesus macaques by penile inoculation with a single SIVenv variant found in ramp-up phase plasma. / Ma, Zhong Min; Keele, Brandon F.; Qureshi, Huma; Stone, Mars; Desilva, Veronique; Fritts, Linda; Lifson, Jeffrey D.; Miller, Chris J.
In: AIDS Research and Human Retroviruses, Vol. 27, No. 12, 01.12.2011, p. 1259-1269.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - SIVmac251 Is inefficiently transmitted to rhesus macaques by penile inoculation with a single SIVenv variant found in ramp-up phase plasma
AU - Ma, Zhong Min
AU - Keele, Brandon F.
AU - Qureshi, Huma
AU - Stone, Mars
AU - Desilva, Veronique
AU - Fritts, Linda
AU - Lifson, Jeffrey D.
AU - Miller, Chris J
PY - 2011/12/1
Y1 - 2011/12/1
N2 - Despite the fact that approximately half of all HIV patients acquire infection through penile exposure, there have been no recent studies of penile SIV transmission in rhesus macaques and the nature of the virus variants transmitted, target cells, and pathways of virus dissemination to systemic lymphoid tissues are not known. Single genome amplification (SGA) and sequencing of HIV-1 RNA in plasma of acutely infected humans allows the identification and enumeration of transmitted/founder viruses responsible for productive systemic infection. Studies using the SGA strategy have shown that intrarectal and intravaginal SIV transmission to macaques recapitulates key features of human HIV transmission. To date, no studies have used the SGA assay to identify transmitted/founder virus(es) in macaques infected after penile SIV exposure. Here we report that SIV can be transmitted by penile SIV exposure. However, similar exposure to a high-dose inoculum infects only about half the animals, which is about 50% less efficient transmission than occurs after vaginal SIV challenge. In addition, only a single SIV env variant established the systemic infection in all five animals that became infected after penile exposure, a result that is consistent with low incidence and few transmitted HIV variants in heterosexually infected men. Our results suggest that the penile transmission of SIVmac251 in rhesus macaques recapitulates the key features of penile HIV-1 transmission and may provide insight into host or viral factors that permit penile transmission and dissemination. Furthermore, this SIV challenge exposure route will be useful in testing vaccines and other prophylactic approaches.
AB - Despite the fact that approximately half of all HIV patients acquire infection through penile exposure, there have been no recent studies of penile SIV transmission in rhesus macaques and the nature of the virus variants transmitted, target cells, and pathways of virus dissemination to systemic lymphoid tissues are not known. Single genome amplification (SGA) and sequencing of HIV-1 RNA in plasma of acutely infected humans allows the identification and enumeration of transmitted/founder viruses responsible for productive systemic infection. Studies using the SGA strategy have shown that intrarectal and intravaginal SIV transmission to macaques recapitulates key features of human HIV transmission. To date, no studies have used the SGA assay to identify transmitted/founder virus(es) in macaques infected after penile SIV exposure. Here we report that SIV can be transmitted by penile SIV exposure. However, similar exposure to a high-dose inoculum infects only about half the animals, which is about 50% less efficient transmission than occurs after vaginal SIV challenge. In addition, only a single SIV env variant established the systemic infection in all five animals that became infected after penile exposure, a result that is consistent with low incidence and few transmitted HIV variants in heterosexually infected men. Our results suggest that the penile transmission of SIVmac251 in rhesus macaques recapitulates the key features of penile HIV-1 transmission and may provide insight into host or viral factors that permit penile transmission and dissemination. Furthermore, this SIV challenge exposure route will be useful in testing vaccines and other prophylactic approaches.
UR - http://www.scopus.com/inward/record.url?scp=82455198719&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=82455198719&partnerID=8YFLogxK
U2 - 10.1089/aid.2011.0090
DO - 10.1089/aid.2011.0090
M3 - Article
C2 - 21732792
AN - SCOPUS:82455198719
VL - 27
SP - 1259
EP - 1269
JO - AIDS Research and Human Retroviruses
JF - AIDS Research and Human Retroviruses
SN - 0889-2229
IS - 12
ER -