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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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Virus recombination obscures compartmentalization of SIV env sequences.Diagrams indicating the positions of predicted recombination breakpoints in compartmentalized monkeys AX89, AX93 and C179 and non-compartmentalized monkey, DA2D. Recombination effects were determined by G.A.R.D. analysis as described. Breakpoint partitions are indicated as vertical lines between inverted triangles. SIV env regions with significant compartmentalization as determined by the partitioned SM test on partitioned sequences, P<0.0002 are highlighted in red boxes.
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ppat-1001293-g005: Virus recombination obscures compartmentalization of SIV env sequences.Diagrams indicating the positions of predicted recombination breakpoints in compartmentalized monkeys AX89, AX93 and C179 and non-compartmentalized monkey, DA2D. Recombination effects were determined by G.A.R.D. analysis as described. Breakpoint partitions are indicated as vertical lines between inverted triangles. SIV env regions with significant compartmentalization as determined by the partitioned SM test on partitioned sequences, P<0.0002 are highlighted in red boxes.

Mentions: Our inability to demonstrate definitive compartmentalization of virus using these strategies led us to consider whether other biologic events might be obscuring compartmentalization. Therefore, we evaluated the possibility that recombination may confound the SM analysis. To assess recombination effects we applied the G.A.R.D. algorithm [48], [56] and found significant levels of recombination (P<0.001) within SIV env, (data not shown). Next, we analyzed our data using a “segmented” SM-test based on env recombination breakpoints (not shown) and found specific regions of the SIV envelope from RMs C179 and AX89 were in fact significantly compartmentalized (P<0.0002, Fig. 5).


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)

Virus recombination obscures compartmentalization of SIV env sequences.Diagrams indicating the positions of predicted recombination breakpoints in compartmentalized monkeys AX89, AX93 and C179 and non-compartmentalized monkey, DA2D. Recombination effects were determined by G.A.R.D. analysis as described. Breakpoint partitions are indicated as vertical lines between inverted triangles. SIV env regions with significant compartmentalization as determined by the partitioned SM test on partitioned sequences, P<0.0002 are highlighted in red boxes.
© Copyright Policy
Related In: Results  -  Collection

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

ppat-1001293-g005: Virus recombination obscures compartmentalization of SIV env sequences.Diagrams indicating the positions of predicted recombination breakpoints in compartmentalized monkeys AX89, AX93 and C179 and non-compartmentalized monkey, DA2D. Recombination effects were determined by G.A.R.D. analysis as described. Breakpoint partitions are indicated as vertical lines between inverted triangles. SIV env regions with significant compartmentalization as determined by the partitioned SM test on partitioned sequences, P<0.0002 are highlighted in red boxes.
Mentions: Our inability to demonstrate definitive compartmentalization of virus using these strategies led us to consider whether other biologic events might be obscuring compartmentalization. Therefore, we evaluated the possibility that recombination may confound the SM analysis. To assess recombination effects we applied the G.A.R.D. algorithm [48], [56] and found significant levels of recombination (P<0.001) within SIV env, (data not shown). Next, we analyzed our data using a “segmented” SM-test based on env recombination breakpoints (not shown) and found specific regions of the SIV envelope from RMs C179 and AX89 were in fact significantly compartmentalized (P<0.0002, Fig. 5).

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