Coinfection with Schistosoma mansoni reactivates viremia in rhesus macaques with chronic simian-human immunodeficiency virus clade C infection

Abstract

We tested the hypothesis that helminth parasite coinfection would intensify viremia and accelerate disease progression in monkeys chronically infected with an R5 simian-human immunodeficiency virus (SHIV) encoding a human immunodeficiency virus type 1 (HIV-1) clade C envelope. Fifteen rhesus monkeys with stable SHIV-1157ip infection were enrolled into a prospective, randomized trial. These seropositive animals had undetectable viral RNA and no signs of immunodeficiency. Seven animals served as virus-only controls; eight animals were exposed to Schistosoma mansoni cercariae. From week 5 after parasite exposure onward, coinfected animals shed eggs in their feces, developed eosinophilia, and had significantly higher mRNA expression of the T-helper type 2 cytokine interleukin-4 (P = 0.001) than animals without schistosomiasis. Compared to virus-only controls, viral replication was significantly increased in coinfected monkeys (P = 0.012), and the percentage of their CD4(+) CD29(+) memory cells decreased over time (P = 0.05). Thus, S. mansoni coinfection significantly increased viral replication and induced T-cell subset alterations in monkeys with chronic SHIV clade C infection.

FIG. 1.

Infection of rhesus macaques with S. mansoni. Eight animals were percutaneously exposed to 500 cercariae. (A) Egg counts in stool samples collected from the S. mansoni-inoculated animals. Data represent the running average of three consecutive values. SEM, standard error of the mean. (B) Percentage of eosinophils in SHIV-1157ip-infected rhesus monkeys with and without concurrent schistosomiasis. In coinfected animals, the percentage of eosinophils rose as a function of time of infection.

FIG. 2.

Ex vivo PBMC cytokine mRNA levels in S. mansoni-infected or control rhesus macaques. Shown is IL-4 (A) and IL-6 (B) mRNA expression relative to the expression of the housekeeping gene coding for PDH in PBMCs from control or schistosome-infected animals at 9 weeks after exposure to cercariae. Data represent column means ± standard deviations. Groups were compared by Wilcoxon's rank-sum test.

FIG. 3.

Acute schistosome infection reactivates latent viral infection. Plasma viral RNA loads in SHIV-1157ip-infected animals with loads that had been low to undetectable (<50 copies/ml) were elevated concurrent with acute S. mansoni infection. Generalized estimation equations were used to compare viral loads between the two groups over time (P = 0.012).

FIG. 4.

Memory T-cell analysis in SHIV-1157ip-infected monkeys. The percentage of CD4⁺ CD29⁺ memory T cells was stable in animals infected with SHIV-1157ip alone but decreased over time in coinfected macaques. Generalized estimation equations were used to model the data collected over time (P = 0.05). The dotted line represents the lower limit of normal for the percentage of CD4⁺ CD29⁺ memory T cells. SEM, standard error of the mean.