Acute Schistosoma mansoni Infection Increases Susceptibility to Systemic SHIV Clade C Infection in Rhesus Macaques after Mucosal Virus Exposure

To test the hypothesis that infection with helmiths may increase host susceptibility to infection with HIV-1, we quantified the amount of a clade C simian-human immunodeficiency virus needed to infect rhesus macaques that had acute Schistosoma mansoni infections. Compared to control animals exposed to virus alone, monkeys with schistosomiasis required exposure to 17-fold lower levels of virus to become infected. The schistosome-infected monkeys also had significantly higher levels of initial virus replication and loss of a certain subset of memory T cells, both predictors of a more rapid progression to immune dysfunction. These results suggest that worm infections may increase the risk of becoming infected with HIV-1 among individuals with viral exposures. Furthermore, they support the idea that control programs for schistosomiasis and perhaps other parasitic worm infections may also be useful in helping to reduce the spread of HIV/AIDS in developing countries where helminths are endemic

Parasitologic and immunologic changes in rhesus macaques infected with <i>Schistosoma mansoni</i>.

<p>(A) Eggs per gram feces in stool samples and percent eosinophils in blood from monkeys that were infected with <i>S. mansoni</i>; (B) IL-4 mRNA expression in PBMC of all <i>S. mansoni</i>-positive rhesus monkeys prior to exposure to SHIV-C. The ratios of IL-4 mRNA copies to mRNA copies of the housekeeping gene PDH are shown. Lines represent group medians. Statistical analysis of data in panel B was performed using the Wilcoxon rank-sum test.</p

Differences in CD4⁺ T cell subsets and cell viral loads between animals with <i>S. mansoni</i>/SHIV-C coinfection and SHIV-C infection alone.

<p>(A) Phenotyping strategy used to separate naïve, central memory (CM), effector memory (EM) and effector memory CD45RA⁺ (EMRA) T cell subsets. Percentages demonstrate T cell subsets for one of the coinfected monkeys. (B) CD4⁺ naïve, CM and EM in coinfected and parasite-free monkeys. (C) SHIV-C RNA detected in CD4⁺ naïve, CM, and EM T cells after sorting. For panels (B) and (C), group means and standard deviations are represented.</p

SHIV-1157ipd3N4 titration.

*<p>This animal was first exposed to a 1∶1000 dilution of the virus. When it was not infected, the monkey was re-exposed to a 1∶5.5 dilution of virus, which was infective.</p