Subsequent malaria enhances virus-specific T cell immunity in SIV-infected Chinese rhesus macaques.

BACKGROUND: Coinfection with HIV and Plasmodium parasites is fairly common, but the sequence of infection with these two pathogens and their impact on disease progression are poorly understood. METHODS: A Chinese rhesus macaque HIV and Plasmodium coinfection model was established to compare the impact of pre-existing and subsequent malaria on the progression of SIV infection. RESULTS: We found that a pre-existing malaria caused animals to produce a greater number of CD4+CCR5+ T cells for SIV replication, resulting in higher viral loads. Conversely, subsequent malaria induced a substantially larger proportion of CD4+CD28highCD95high central memory T cells and a stronger SIV-specific T cell response, maintained the repertoire diversity of SIV-specific T cell receptors, and generated new SIV-specific T cell clonotypes to trace SIV antigenic variation, resulting in improved survival of SIV-infected animals. CONCLUSION: The complex outcomes of this study may have important implications for research on human HIV and malaria coinfection. The infection order of the two pathogens (HIV and malaria parasites) should be emphasized. Video abstract.

SIV infection aggravates malaria in a Chinese rhesus monkey coinfection model.

BACKGROUND: The co-occurrence of human immunodeficiency virus (HIV) infection and malaria in humans in endemic areas raises the question of whether one of these infections affects the course of the other. Although epidemiological studies have shown the impact of HIV infection on malaria, the mechanism(s) are not yet fully understood. Using a Chinese rhesus macaque coinfection model with simian immunodeficiency virus (SIV) and Plasmodium cynomolgi (Pc) malaria, we investigated the effect of concurrent SIV infection on the course of malaria and the underlying immunological mechanism(s). METHODS: We randomly assigned ten Chinese rhesus monkeys to two groups based on body weight and age. The SIV-Pc coinfection animals (S + P group) were infected intravenously with SIVmac251 eight weeks prior to malaria infection, and the control animals (P group) were infected intravenously with only Pc-infected red blood cells. After malaria was cured with chloroquine phosphate, we also initiated a secondary malaria infection that lasted 4 weeks. We monitored body weight, body temperature and parasitemia, measured SIV viral loads, hemoglobin and neopterin, and tracked the CD4+, CD8+, and CD4+ memory subpopulations, Ki67 and apoptosis by flow cytometry. Then, we compared these parameters between the two groups. RESULTS: The animals infected with SIV prior to Pc infection exhibited more severe malaria symptoms characterized by longer episodes, higher parasitemia, more severe anemia, greater body weight loss and higher body temperature than the animals infected with Pc alone. Concurrent SIV infection also impaired immune protection against the secondary Pc challenge infection. The coinfected animals showed a reduced B cell response to Pc malaria and produced lower levels of Pc-specific antibodies. In addition, compared to the animals subjected to Pc infection alone, the animals coinfected with SIV and Pc had suppressed total CD4+ T cells, CD4+CD28highCD95high central memory T cells, and CD4+CD28lowCD95- naïve T cells, which may result from the imbalanced immune activation and faster CD4+ T cell turnover in coinfected animals. CONCLUSIONS: SIV infection aggravates malaria physiologically and immunologically in Chinese rhesus monkeys. This nonhuman primate SIV and Pc malaria coinfection model might be a useful tool for investigating human HIV and malaria coinfection and developing effective therapeutics.