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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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Related in: MedlinePlus

Source of SIV in the semen-associated cell fraction.(A) Semen virus DNA levels in the control and Gag-Pol vaccinated monkeys 14 days after virus challenge. The comparisons of the data from the Gag-Pol vaccinated and control groups were analyzed using the Mann-Whitney non-parametric T-test. The absolute number of SIV gag DNA copies was calculated as described previously [44], and is shown as log-transformed copies per 1×105 semen-associated cells. (B) Phylogeny of SIV env in monkey CK7J, 14 days after virus challenge with blood plasma virus, semen plasma and semen cell-associated virus indicated.
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ppat-1001293-g003: Source of SIV in the semen-associated cell fraction.(A) Semen virus DNA levels in the control and Gag-Pol vaccinated monkeys 14 days after virus challenge. The comparisons of the data from the Gag-Pol vaccinated and control groups were analyzed using the Mann-Whitney non-parametric T-test. The absolute number of SIV gag DNA copies was calculated as described previously [44], and is shown as log-transformed copies per 1×105 semen-associated cells. (B) Phylogeny of SIV env in monkey CK7J, 14 days after virus challenge with blood plasma virus, semen plasma and semen cell-associated virus indicated.

Mentions: We next explored the source of virus found in the male genital tract at the time of peak viremia. By day 14 following infection, significant levels of cell-free virus RNA and cell-associated provirus are present in the semen of both control and vaccinated animals (Fig. 3A) [44]. Examination of SIV env sequences from seminal plasma and semen-associated cells from monkey CK7J using NJ- tree parameters (Fig. 3B) indicated that several clusters of monotypic cell-free virus were identical in sequence to the semen provirus. Moreover, several clusters of cell-free and cell-associated virus in the genital tract of this monkey were phylogenetically indistinguishable from SIV env sequences derived cell-free and cell-associated virus from the blood. These data argue that in early SIV infection, during the period of peak viremia, there is significant virus gene flow between anatomic compartments. There are also significant levels of cell-associated and cell-free sources of virus present early in infection that may constitute a source of transmissible virus.


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)

Source of SIV in the semen-associated cell fraction.(A) Semen virus DNA levels in the control and Gag-Pol vaccinated monkeys 14 days after virus challenge. The comparisons of the data from the Gag-Pol vaccinated and control groups were analyzed using the Mann-Whitney non-parametric T-test. The absolute number of SIV gag DNA copies was calculated as described previously [44], and is shown as log-transformed copies per 1×105 semen-associated cells. (B) Phylogeny of SIV env in monkey CK7J, 14 days after virus challenge with blood plasma virus, semen plasma and semen cell-associated virus indicated.
© Copyright Policy
Related In: Results  -  Collection

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

ppat-1001293-g003: Source of SIV in the semen-associated cell fraction.(A) Semen virus DNA levels in the control and Gag-Pol vaccinated monkeys 14 days after virus challenge. The comparisons of the data from the Gag-Pol vaccinated and control groups were analyzed using the Mann-Whitney non-parametric T-test. The absolute number of SIV gag DNA copies was calculated as described previously [44], and is shown as log-transformed copies per 1×105 semen-associated cells. (B) Phylogeny of SIV env in monkey CK7J, 14 days after virus challenge with blood plasma virus, semen plasma and semen cell-associated virus indicated.
Mentions: We next explored the source of virus found in the male genital tract at the time of peak viremia. By day 14 following infection, significant levels of cell-free virus RNA and cell-associated provirus are present in the semen of both control and vaccinated animals (Fig. 3A) [44]. Examination of SIV env sequences from seminal plasma and semen-associated cells from monkey CK7J using NJ- tree parameters (Fig. 3B) indicated that several clusters of monotypic cell-free virus were identical in sequence to the semen provirus. Moreover, several clusters of cell-free and cell-associated virus in the genital tract of this monkey were phylogenetically indistinguishable from SIV env sequences derived cell-free and cell-associated virus from the blood. These data argue that in early SIV infection, during the period of peak viremia, there is significant virus gene flow between anatomic compartments. There are also significant levels of cell-associated and cell-free sources of virus present early in infection that may constitute a source of transmissible virus.

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