Schistosoma mansoni enhances host susceptibility to mucosal but not intravenous challenge by R5 clade C SHIV

Siddappa Nagadenahalli Byrareddy, Girish Hemashettar, Vivekanandan Shanmuganathan, Amma A. Semenya, Elizabeth D. Sweeney, Katherine S. Paul, Sandra J. Lee, W. Evan Secor, Ruth M. Ruprecht

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Background: The high prevalence of HIV-1/AIDS in areas endemic for schistosomiasis and other helminthic infections has led to the hypothesis that parasites increase host susceptibility to immunodeficiency virus infection. We previously showed that rhesus macaques (RM) with active schistosomiasis were significantly more likely to become systemically infected after intrarectal (i.r.) exposure to an R5-tropic clade C simian-human immunodeficiency virus (SHIV-C) than were parasite-free controls. However, we could not address whether this was due to systemic or mucosal effects. If systemic immunoactivation resulted in increased susceptibility to SHIV-C acquisition, a similarly large difference in host susceptibility would be seen after intravenous (i.v.) SHIV-C challenge. Conversely, if increased host susceptibility was due to parasite-induced immunoactivation at the mucosal level, i.v. SHIV-C challenge would not result in significant differences between parasitized and parasite-free monkeys. Methods and Findings: We enrolled two groups of RM and infected one group with Schistosoma mansoni; the other group was left parasite-free. Both groups were challenged i.v. with decreasing doses of SHIV-C. No statistically significant differences in 50% animal infectious doses (AID50) or peak viremia were seen between the two groups. These data strongly contrast the earlier i.r. SHIV-C challenge (using the same virus stock) in the presence/absence of parasites, where we noted a 17-fold difference in AID50 and one log higher peak viremia in parasitized monkeys (P<0.001 for both). The lack of significant differences after the i.v. challenge implies that the increased host susceptibility is predominantly due to parasite-mediated mucosal upregulation of virus replication and spread, rather than systemic effects. Conclusions: The major impact of schistosome-induced increased host susceptibility is at the mucosal level. Given that >90% of all new HIV-1 infections worldwide are acquired through mucosal contact, parasitic infections that inflame mucosae may play an important role in the spread of HIV-1.

Original languageEnglish (US)
Article numbere1270
JournalPLoS Neglected Tropical Diseases
Volume5
Issue number8
DOIs
StatePublished - Aug 1 2011

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Schistosoma mansoni
Parasites
HIV-1
Viremia
Schistosomiasis
Macaca mulatta
Haplorhini
Communicable Disease Control
Simian Immunodeficiency Virus
Parasitic Diseases
Virus Diseases
HIV Infections
Mucous Membrane
Acquired Immunodeficiency Syndrome
HIV
Viruses
Infection

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

Schistosoma mansoni enhances host susceptibility to mucosal but not intravenous challenge by R5 clade C SHIV. / Byrareddy, Siddappa Nagadenahalli; Hemashettar, Girish; Shanmuganathan, Vivekanandan; Semenya, Amma A.; Sweeney, Elizabeth D.; Paul, Katherine S.; Lee, Sandra J.; Secor, W. Evan; Ruprecht, Ruth M.

In: PLoS Neglected Tropical Diseases, Vol. 5, No. 8, e1270, 01.08.2011.

Research output: Contribution to journalArticle

Byrareddy, SN, Hemashettar, G, Shanmuganathan, V, Semenya, AA, Sweeney, ED, Paul, KS, Lee, SJ, Secor, WE & Ruprecht, RM 2011, 'Schistosoma mansoni enhances host susceptibility to mucosal but not intravenous challenge by R5 clade C SHIV', PLoS Neglected Tropical Diseases, vol. 5, no. 8, e1270. https://doi.org/10.1371/journal.pntd.0001270
Byrareddy, Siddappa Nagadenahalli ; Hemashettar, Girish ; Shanmuganathan, Vivekanandan ; Semenya, Amma A. ; Sweeney, Elizabeth D. ; Paul, Katherine S. ; Lee, Sandra J. ; Secor, W. Evan ; Ruprecht, Ruth M. / Schistosoma mansoni enhances host susceptibility to mucosal but not intravenous challenge by R5 clade C SHIV. In: PLoS Neglected Tropical Diseases. 2011 ; Vol. 5, No. 8.
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abstract = "Background: The high prevalence of HIV-1/AIDS in areas endemic for schistosomiasis and other helminthic infections has led to the hypothesis that parasites increase host susceptibility to immunodeficiency virus infection. We previously showed that rhesus macaques (RM) with active schistosomiasis were significantly more likely to become systemically infected after intrarectal (i.r.) exposure to an R5-tropic clade C simian-human immunodeficiency virus (SHIV-C) than were parasite-free controls. However, we could not address whether this was due to systemic or mucosal effects. If systemic immunoactivation resulted in increased susceptibility to SHIV-C acquisition, a similarly large difference in host susceptibility would be seen after intravenous (i.v.) SHIV-C challenge. Conversely, if increased host susceptibility was due to parasite-induced immunoactivation at the mucosal level, i.v. SHIV-C challenge would not result in significant differences between parasitized and parasite-free monkeys. Methods and Findings: We enrolled two groups of RM and infected one group with Schistosoma mansoni; the other group was left parasite-free. Both groups were challenged i.v. with decreasing doses of SHIV-C. No statistically significant differences in 50{\%} animal infectious doses (AID50) or peak viremia were seen between the two groups. These data strongly contrast the earlier i.r. SHIV-C challenge (using the same virus stock) in the presence/absence of parasites, where we noted a 17-fold difference in AID50 and one log higher peak viremia in parasitized monkeys (P<0.001 for both). The lack of significant differences after the i.v. challenge implies that the increased host susceptibility is predominantly due to parasite-mediated mucosal upregulation of virus replication and spread, rather than systemic effects. Conclusions: The major impact of schistosome-induced increased host susceptibility is at the mucosal level. Given that >90{\%} of all new HIV-1 infections worldwide are acquired through mucosal contact, parasitic infections that inflame mucosae may play an important role in the spread of HIV-1.",
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AU - Semenya, Amma A.

AU - Sweeney, Elizabeth D.

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