title: Evidence for an increased risk of transmission of simian immunodeficiency virus and malaria in a rhesus macaque coinfection model.
abstract: In sub-Saharan Africa, HIV-1 infection frequently occurs in the context of other coinfecting pathogens, most importantly, Mycobacterium tuberculosis and malaria parasites. The consequences are often devastating, resulting in enhanced morbidity and mortality. Due to the large number of confounding factors influencing pathogenesis in coinfected people, we sought to develop a nonhuman primate model of simian immunodeficiency virus (SIV)-malaria coinfection. In sub-Saharan Africa, Plasmodium falciparum is the most common malaria parasite and is responsible for most malaria-induced deaths. The simian malaria parasite Plasmodium fragile can induce clinical symptoms, including cerebral malaria in rhesus macaques, that resemble those of P. falciparum infection in humans. Thus, based on the well-characterized rhesus macaque model of SIV infection, this study reports the development of a novel rhesus macaque SIV-P. fragile coinfection model to study human HIV-P. falciparum coinfection. Using this model, we show that coinfection is associated with an increased, although transient, risk of both HIV and malaria transmission. Specifically, SIV-P. fragile coinfected macaques experienced an increase in SIV viremia that was temporarily associated with an increase in potential SIV target cells and systemic immune activation during acute parasitemia. Conversely, primary parasitemia in SIV-P. fragile coinfected animals resulted in higher gametocytemia that subsequently translated into higher oocyst development in mosquitoes. To our knowledge, this is the first animal model able to recapitulate the increased transmission risk of both HIV and malaria in coinfected humans. Therefore, this model could serve as an essential tool to elucidate distinct immunological, virological, and/or parasitological parameters underlying disease exacerbation in HIV-malaria coinfected people.
authors.affiliation: 1California National Primate Research Center, University of California at Davis, County Road 98/Hutchison Drive, Davis, California 95616, USA.
authors.forename: Kristin A
authors.initials: KA
authors.lastname: Trott
authors.forename: Jennifer Y
authors.initials: JY
authors.lastname: Chau
authors.forename: Michael G
authors.initials: MG
authors.lastname: Hudgens
authors.forename: Jason
authors.initials: J
authors.lastname: Fine
authors.forename: Chelu K
authors.initials: CK
authors.lastname: Mfalila
authors.forename: Ross P
authors.initials: RP
authors.lastname: Tarara
authors.forename: William E
authors.initials: WE
authors.lastname: Collins
authors.forename: Joann
authors.initials: J
authors.lastname: Sullivan
authors.forename: Shirley
authors.initials: S
authors.lastname: Luckhart
authors.forename: Kristina
authors.initials: K
authors.lastname: Abel
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D008253:Macaca mulatta; D008288:Malaria / Q000150:complications* / Q000635:transmission*; D008297:Male; D018512:Parasitemia / Q000150:complications; D010963:Plasmodium falciparum / Q000302:isolation & purification / Q000472:pathogenicity*; D018419:Primate Diseases / Q000635:transmission; D016097:Simian Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000635:transmission*; D015302:Simian Immunodeficiency Virus / Q000302:isolation & purification / Q000472:pathogenicity*; D014766:Viremia / Q000150:complications