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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

Intermixing of blood- and semen-derived env sequences during peak SIV replication.Neighbor-joining trees from vaccinated monkeys (A) AX93, (B) AY47 and control monkeys (C) CK7J and (D) CM8X 2 weeks after challenge with a sequence-defined SIVmac251 challenge stock (stock sequences denoted in black).
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ppat-1001293-g001: Intermixing of blood- and semen-derived env sequences during peak SIV replication.Neighbor-joining trees from vaccinated monkeys (A) AX93, (B) AY47 and control monkeys (C) CK7J and (D) CM8X 2 weeks after challenge with a sequence-defined SIVmac251 challenge stock (stock sequences denoted in black).

Mentions: SIV env sequences were first generated from both the blood and semen of 14 rhesus monkeys (7 vaccinated and 7 control) from specimens obtained 2 weeks following infection. The genetic diversity of the virus from each anatomic compartment of each monkey was calculated as the average pair-wise genetic distance of SIV env within each semen or blood population from the inoculum consensus. Data from the vaccinated and control animals were analyzed independently. Since these represented analyses of sequence from virus obtained very early after infection, little divergence was seen from the founder viruses that initiated infection in each monkey (Table 1). Moreover, we observed little genetic diversity between sequences of blood and semen amplicons at this early time point after challenge, representative examples from 4 monkeys (2 control, 2 vaccinated) are shown (Fig. 1). Among the sequences from the blood, we observed no difference in average pairwise env distance from the inoculum consensus per animal between vaccinees (0.29% versus 0.28% respectively, P = 0.9). The sequence divergence for all week 2 semen isolates were not significantly different in control and vaccinated monkeys, with a mean distance among control animals of 0.27% and 0.15% among vaccinated monkeys (P = 0.4). These differences are consistent with the lower levels of viral replication in the vaccinated group [44].


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)

Intermixing of blood- and semen-derived env sequences during peak SIV replication.Neighbor-joining trees from vaccinated monkeys (A) AX93, (B) AY47 and control monkeys (C) CK7J and (D) CM8X 2 weeks after challenge with a sequence-defined SIVmac251 challenge stock (stock sequences denoted in black).
© Copyright Policy
Related In: Results  -  Collection

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

ppat-1001293-g001: Intermixing of blood- and semen-derived env sequences during peak SIV replication.Neighbor-joining trees from vaccinated monkeys (A) AX93, (B) AY47 and control monkeys (C) CK7J and (D) CM8X 2 weeks after challenge with a sequence-defined SIVmac251 challenge stock (stock sequences denoted in black).
Mentions: SIV env sequences were first generated from both the blood and semen of 14 rhesus monkeys (7 vaccinated and 7 control) from specimens obtained 2 weeks following infection. The genetic diversity of the virus from each anatomic compartment of each monkey was calculated as the average pair-wise genetic distance of SIV env within each semen or blood population from the inoculum consensus. Data from the vaccinated and control animals were analyzed independently. Since these represented analyses of sequence from virus obtained very early after infection, little divergence was seen from the founder viruses that initiated infection in each monkey (Table 1). Moreover, we observed little genetic diversity between sequences of blood and semen amplicons at this early time point after challenge, representative examples from 4 monkeys (2 control, 2 vaccinated) are shown (Fig. 1). Among the sequences from the blood, we observed no difference in average pairwise env distance from the inoculum consensus per animal between vaccinees (0.29% versus 0.28% respectively, P = 0.9). The sequence divergence for all week 2 semen isolates were not significantly different in control and vaccinated monkeys, with a mean distance among control animals of 0.27% and 0.15% among vaccinated monkeys (P = 0.4). These differences are consistent with the lower levels of viral replication in the vaccinated group [44].

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