Readily acquired secondary infections of human and simian immunodeficiency viruses following single intravenous exposure in non-human primates.
Accumulating evidence suggests that exposed individuals may acquire multiple human immunodeficiency virus (HIV) infections more frequently than originally believed. As a result, circulating recombinant forms of HIV are emerging that are of particular concern in the AIDS epidemic and HIV vaccine development efforts. The aim of this study was to determine under what conditions secondary or superinfections of HIV or simian immunodeficiency virus (SIV) may be acquired under controlled settings in well-defined, non-human primate models. Retrospective analysis of macaques that had acquired apparent immunity upon infection with a defined attenuated SIV(mac) strain revealed that eight out of eight animals that were secondarily exposed to a new virus variant became infected with the new virus strain, but at low levels. Interestingly, similarly high frequencies of secondary infections were observed after early (4 months), as well as late (5 years), exposure following primary infection. As possible causes of susceptibility to secondary infections, perturbations in the immune system associated with exacerbated infections were then investigated prospectively. Results revealed that short-term immune-suppression therapy did not increase susceptibility to secondary infections. Taken together, data suggested that neither early- nor late-exposure immune-suppressive events following primary infection accounted for the observed high incidence of secondary infections. With HIV-1, the question of whether secondary infections with very closely related viral variants could occur in the chimpanzee model was addressed. In both animal models, secondary infections were confirmed, notably with relatively closely related SIV(mac) or HIV-1 strains, following a single exposure to the secondary virus strain. These findings reveal that secondary lentiviral infections may be acquired readily during different stages of primary infection, in contrast to co-infections, which are acquired at the moment of initial infection.
Haaft
Peter Ten
PT
Department of Virology, Biomedical Primate Research Centre, PO Box 3306, 2280 GH Rijswijk, The Netherlands.
Verschoor
Ernst J
EJ
Department of Virology, Biomedical Primate Research Centre, PO Box 3306, 2280 GH Rijswijk, The Netherlands.
Verstrepen
Babs
B
Department of Virology, Biomedical Primate Research Centre, PO Box 3306, 2280 GH Rijswijk, The Netherlands.
Niphuis
Henk
H
Department of Virology, Biomedical Primate Research Centre, PO Box 3306, 2280 GH Rijswijk, The Netherlands.
Dubbes
Rob
R
Department of Virology, Biomedical Primate Research Centre, PO Box 3306, 2280 GH Rijswijk, The Netherlands.
Koornstra
Wim
W
Department of Virology, Biomedical Primate Research Centre, PO Box 3306, 2280 GH Rijswijk, The Netherlands.
Bogers
Willy
W
Department of Virology, Biomedical Primate Research Centre, PO Box 3306, 2280 GH Rijswijk, The Netherlands.
Rosenwirth
Brigitte
B
Department of Virology, Biomedical Primate Research Centre, PO Box 3306, 2280 GH Rijswijk, The Netherlands.
Heeney
Jonathan L
JL
Department of Virology, Biomedical Primate Research Centre, PO Box 3306, 2280 GH Rijswijk, The Netherlands.
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D000818:Animals; D015497:HIV-1; D007108:Immune Tolerance; D008253:Macaca mulatta; D002679:Pan troglodytes; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D013997:Time Factors