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Genital tract sequestration of SIV following acute infection.

Whitney JB, Hraber PT, Luedemann C, Giorgi EE, Daniels MG, Bhattacharya T, Rao SS, Mascola JR, Nabel GJ, Korber BT, Letvin NL - PLoS Pathog. (2011)

Bottom Line: We characterized the evolution of simian immunodeficiency virus (SIV) in the male genital tract by examining blood- and semen-associated virus from experimentally and sham vaccinated rhesus monkeys during primary infection.At the time of peak virus replication, SIV sequences were intermixed between the blood and semen supporting a scenario of high-level virus "spillover" into the male genital tract.These findings suggest that SIV replication in the male genital tract evolves to compartmentalization after peak viremia resolves.

View Article: PubMed Central - PubMed

Affiliation: Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA. jwhitne2@bidmc.harvard.edu

ABSTRACT
We characterized the evolution of simian immunodeficiency virus (SIV) in the male genital tract by examining blood- and semen-associated virus from experimentally and sham vaccinated rhesus monkeys during primary infection. At the time of peak virus replication, SIV sequences were intermixed between the blood and semen supporting a scenario of high-level virus "spillover" into the male genital tract. However, at the time of virus set point, compartmentalization was apparent in 4 of 7 evaluated monkeys, likely as a consequence of restricted virus gene flow between anatomic compartments after the resolution of primary viremia. These findings suggest that SIV replication in the male genital tract evolves to compartmentalization after peak viremia resolves.

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Association and threshold-effect between SIV DNA, and RNA levels in blood and semen.Cell-associated SIV trafficking into the male genital tract during peak and set point SIV infection. The comparisons of the data from the Gag-Pol vaccinated and control groups were analyzed using the Mann-Whitney non-parametric U-test. The absolute number of SIV gag DNA copies was calculated as described previously, and is shown as log-transformed copies per 1×105 semen-associated cells. (A). Association and threshold effect between levels in blood plasma and seminal plasma from both vaccinated and control monkeys (B). Adapted from Whitney et al. [44].
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ppat-1001293-g007: Association and threshold-effect between SIV DNA, and RNA levels in blood and semen.Cell-associated SIV trafficking into the male genital tract during peak and set point SIV infection. The comparisons of the data from the Gag-Pol vaccinated and control groups were analyzed using the Mann-Whitney non-parametric U-test. The absolute number of SIV gag DNA copies was calculated as described previously, and is shown as log-transformed copies per 1×105 semen-associated cells. (A). Association and threshold effect between levels in blood plasma and seminal plasma from both vaccinated and control monkeys (B). Adapted from Whitney et al. [44].

Mentions: To explore the mechanisms responsible for this changing pattern of viral evolution in the male genital tract, we evaluated 2 virologic correlates associated with compartmentalization. First, we observed that cell-associated virus levels in the male genital tract during peak infection are diminished significantly in the animals by week 8 following infection (Fig. 7A). Second, cell-free virus levels in the semen are also significantly diminished between weeks 2 and 16 following infection (Fig. 7B). In fact, these cell-free virus data demonstrate a threshold effect whereby viral RNA is only detectable in the seminal plasma when virus levels in the blood plasma exceed 104 RNA copies/ml. The coincidence of the resolution of primary viremia with the decrease in levels of virus in genital secretions suggest that the dramatic fall in virus replication, with the accompanying restriction of gene flow, during this early period of infection underlies the development of viral compartmentalization.


Genital tract sequestration of SIV following acute infection.

Whitney JB, Hraber PT, Luedemann C, Giorgi EE, Daniels MG, Bhattacharya T, Rao SS, Mascola JR, Nabel GJ, Korber BT, Letvin NL - PLoS Pathog. (2011)

Association and threshold-effect between SIV DNA, and RNA levels in blood and semen.Cell-associated SIV trafficking into the male genital tract during peak and set point SIV infection. The comparisons of the data from the Gag-Pol vaccinated and control groups were analyzed using the Mann-Whitney non-parametric U-test. The absolute number of SIV gag DNA copies was calculated as described previously, and is shown as log-transformed copies per 1×105 semen-associated cells. (A). Association and threshold effect between levels in blood plasma and seminal plasma from both vaccinated and control monkeys (B). Adapted from Whitney et al. [44].
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3040679&req=5

ppat-1001293-g007: Association and threshold-effect between SIV DNA, and RNA levels in blood and semen.Cell-associated SIV trafficking into the male genital tract during peak and set point SIV infection. The comparisons of the data from the Gag-Pol vaccinated and control groups were analyzed using the Mann-Whitney non-parametric U-test. The absolute number of SIV gag DNA copies was calculated as described previously, and is shown as log-transformed copies per 1×105 semen-associated cells. (A). Association and threshold effect between levels in blood plasma and seminal plasma from both vaccinated and control monkeys (B). Adapted from Whitney et al. [44].
Mentions: To explore the mechanisms responsible for this changing pattern of viral evolution in the male genital tract, we evaluated 2 virologic correlates associated with compartmentalization. First, we observed that cell-associated virus levels in the male genital tract during peak infection are diminished significantly in the animals by week 8 following infection (Fig. 7A). Second, cell-free virus levels in the semen are also significantly diminished between weeks 2 and 16 following infection (Fig. 7B). In fact, these cell-free virus data demonstrate a threshold effect whereby viral RNA is only detectable in the seminal plasma when virus levels in the blood plasma exceed 104 RNA copies/ml. The coincidence of the resolution of primary viremia with the decrease in levels of virus in genital secretions suggest that the dramatic fall in virus replication, with the accompanying restriction of gene flow, during this early period of infection underlies the development of viral compartmentalization.

Bottom Line: We characterized the evolution of simian immunodeficiency virus (SIV) in the male genital tract by examining blood- and semen-associated virus from experimentally and sham vaccinated rhesus monkeys during primary infection.At the time of peak virus replication, SIV sequences were intermixed between the blood and semen supporting a scenario of high-level virus "spillover" into the male genital tract.These findings suggest that SIV replication in the male genital tract evolves to compartmentalization after peak viremia resolves.

View Article: PubMed Central - PubMed

Affiliation: Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA. jwhitne2@bidmc.harvard.edu

ABSTRACT
We characterized the evolution of simian immunodeficiency virus (SIV) in the male genital tract by examining blood- and semen-associated virus from experimentally and sham vaccinated rhesus monkeys during primary infection. At the time of peak virus replication, SIV sequences were intermixed between the blood and semen supporting a scenario of high-level virus "spillover" into the male genital tract. However, at the time of virus set point, compartmentalization was apparent in 4 of 7 evaluated monkeys, likely as a consequence of restricted virus gene flow between anatomic compartments after the resolution of primary viremia. These findings suggest that SIV replication in the male genital tract evolves to compartmentalization after peak viremia resolves.

Show MeSH
Related in: MedlinePlus