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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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Compartmentalization of blood- and semen-derived env sequences during peak SIV replication in monkey AX89.NJ tree from control animal AX89, 2 weeks after challenge using a sequence-defined SIVmac251 stock (denoted in black).
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ppat-1001293-g002: Compartmentalization of blood- and semen-derived env sequences during peak SIV replication in monkey AX89.NJ tree from control animal AX89, 2 weeks after challenge using a sequence-defined SIVmac251 stock (denoted in black).

Mentions: While we did not observe topological evidence for virus compartmentalization between the semen and blood during early infection in any of the 14 monkeys analyzed, compartmentalization effects were also assessed using the SM test. Applying this metric, we observed no evidence of virus sequestration in week 2 blood- or semen-derived sequences in 13 of the 14 monkeys (Table 2). Control monkey AX89 had compartmentalized semen env sequences (s = 14, P<0.0001) (Fig. 2). However, the presence of large numbers of identical monotypic sequences might bias statistical measures of compartmentalization [54], [55]. To ensure that the large numbers of isogenic sequences in the semen of AX89 were not confounding this statistical analysis, we conducted a secondary analysis that collapsed all equivalently rooted monotypic sequences to a single representative env taxon. We then applied the same SM test to the normalized set of env sequences from monkey AX89. This modified analysis also indicated significant compartmentalization between SIV env in the blood and the male genital tract of monkey AX89 (s = 14, P = 0.0007). Therefore, there was weak evidence for virus compartmentalization in only 1 of the 14 monkeys by 2 weeks post-infection.


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)

Compartmentalization of blood- and semen-derived env sequences during peak SIV replication in monkey AX89.NJ tree from control animal AX89, 2 weeks after challenge using a sequence-defined SIVmac251 stock (denoted in black).
© Copyright Policy
Related In: Results  -  Collection

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

ppat-1001293-g002: Compartmentalization of blood- and semen-derived env sequences during peak SIV replication in monkey AX89.NJ tree from control animal AX89, 2 weeks after challenge using a sequence-defined SIVmac251 stock (denoted in black).
Mentions: While we did not observe topological evidence for virus compartmentalization between the semen and blood during early infection in any of the 14 monkeys analyzed, compartmentalization effects were also assessed using the SM test. Applying this metric, we observed no evidence of virus sequestration in week 2 blood- or semen-derived sequences in 13 of the 14 monkeys (Table 2). Control monkey AX89 had compartmentalized semen env sequences (s = 14, P<0.0001) (Fig. 2). However, the presence of large numbers of identical monotypic sequences might bias statistical measures of compartmentalization [54], [55]. To ensure that the large numbers of isogenic sequences in the semen of AX89 were not confounding this statistical analysis, we conducted a secondary analysis that collapsed all equivalently rooted monotypic sequences to a single representative env taxon. We then applied the same SM test to the normalized set of env sequences from monkey AX89. This modified analysis also indicated significant compartmentalization between SIV env in the blood and the male genital tract of monkey AX89 (s = 14, P = 0.0007). Therefore, there was weak evidence for virus compartmentalization in only 1 of the 14 monkeys by 2 weeks post-infection.

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