Altered immune responses in rhesus macaques co-infected with SIV and Plasmodium cynomolgi: an animal model for coincident AIDS and relapsing malaria.
BACKGROUND
Dual epidemics of the malaria parasite Plasmodium and HIV-1 in sub-Saharan Africa and Asia present a significant risk for co-infection in these overlapping endemic regions. Recent studies of HIV/Plasmodium falciparum co-infection have reported significant interactions of these pathogens, including more rapid CD4+ T cell loss, increased viral load, increased immunosuppression, and increased episodes of clinical malaria. Here, we describe a novel rhesus macaque model for co-infection that supports and expands upon findings in human co-infection studies and can be used to identify interactions between these two pathogens.


RESULTS
Five rhesus macaques were infected with P. cynomolgi and, following three parasite relapses, with SIV. Compared to macaques infected with SIV alone, co-infected animals had, as a group, decreased survival time and more rapid declines in markers for SIV progression, including peripheral CD4+ T cells and CD4+/CD8+ T cell ratios. The naïve CD4+ T cell pool of the co-infected animals was depleted more rapidly than animals infected with SIV alone. The co-infected animals also failed to generate proliferative responses to parasitemia by CD4+ and CD8+ T cells as well as B cells while also having a less robust anti-parasite and altered anti-SIV antibody response.


CONCLUSIONS
These data suggest that infection with both SIV and Plasmodium enhances SIV-induced disease progression and impairs the anti-Plasmodium immune response. These data support findings in HIV/Plasmodium co-infection studies. This animal model can be used to further define impacts of lentivirus and Plasmodium co-infection and guide public health and therapeutic interventions.
Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, Louisiana, United States of America. jeff.koehler@amedd.army.mil
Jeffrey W
JW
Koehler
Michael
M
Bolton
Amanda
A
Rollins
Kirsten
K
Snook
Eileen
E
deHaro
Elizabeth
E
Henson
Linda
L
Rogers
Louis N
LN
Martin
Donald J
DJ
Krogstad
Mark A
MA
James
Janet
J
Rice
Billie
B
Davison
Ronald S
RS
Veazey
Ramesh
R
Prabhu
Angela M
AM
Amedee
Robert F
RF
Garry
Frank B
FB
Cogswell
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000821:virology; D004195:Disease Models, Animal; D018450:Disease Progression; D016086:Lentivirus / Q000235:genetics; D008253:Macaca mulatta; D008288:Malaria / Q000150:complications* / Q000276:immunology*; D016789:Plasmodium cynomolgi / Q000378:metabolism*; D012008:Recurrence; D012306:Risk; D016097:Simian Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000378:metabolism*; D034101:Sporozoites / Q000378:metabolism; D019562:Viral Load