Related Experiment Videos
Humoral response to SIV/SMM infection in macaque and mangabey monkeys
P N Fultz1, R B Stricker, H M McClure
1Yerkes Regional Primate Research Center, Emory University, Atlanta, Georgia 30322.
Abstract:
Natural infection of sooty mangabey monkeys with simian immunodeficiency virus, designated SIV/SMM, results in long-term persistent infections with little or no disease. In contrast, experimental infection of macaques with isolates of SIV/SMM induces chronic and progressive disease that terminates in an AIDS-like illness and death in most animals. To determine whether antibodies might be important in preventing the development of disease in mangabeys or progression of disease in macaques, humoral immune responses to SIV/SMM were compared in 13 macaques infected for up to 43 months and in infected and uninfected mangabeys selected at random from among a breeding colony. Total SIV/SMM-specific antibody titers, profiles of antibodies to specific viral proteins, neutralizing antibodies that inhibited infectivity of cell-free virus or syncytia formation, antibodies that inhibited reverse transcriptase activity, and antibodies to lymphocyte cell-surface antigens were assessed. The results indicated that in macaques the magnitude of the SIV/SMM-specific antibody response and progression of disease were functions of virus load. Surprisingly, asymptomatic mangabeys also had high virus loads with, on average, lower antibody titers than macaques. In both species, the presence of neutralizing antibodies or antibodies that inhibited SIV/SMM reverse transcriptase activity did not correlate with protection from clinical disease. A correlation was observed, however, between the development of disease and the presence of antibodies to an 18-kDa protein that is found on the surface of activated lymphocytes and appears to be related to histone H2B. A similar correlation has been observed in association with HIV infection in humans, suggesting that some manifestations of both human and simian AIDS may result from autoimmune reactions.
Insights
Sooty mangabeys infected with simian immunodeficiency virus (SIV/SMM) remain healthy, unlike macaques which develop AIDS. Antibody responses did not prevent disease, but antibodies to an 18-kDa lymphocyte protein correlated with disease development in both species.
Area of Science:
- Immunology
- Virology
- Primatology
Background:
- Sooty mangabeys exhibit natural resistance to simian immunodeficiency virus (SIV/SMM) infection, remaining asymptomatic.
- Experimental SIV/SMM infection in macaques leads to progressive, AIDS-like illness and death.
- The role of humoral immunity in disease pathogenesis and protection remains unclear.
Purpose of the Study:
- To compare humoral immune responses to SIV/SMM in infected macaques and sooty mangabeys.
- To investigate the correlation between antibody profiles and disease progression or protection.
- To identify potential antibody targets associated with AIDS-like illness in SIV-infected primates.
Main Methods:
- Assessment of SIV/SMM-specific antibody titers and profiles against viral proteins.
- Evaluation of neutralizing antibodies and antibodies inhibiting reverse transcriptase activity.
- Analysis of antibodies targeting lymphocyte cell-surface antigens in infected macaques and mangabeys.
Main Results:
- Both macaques and asymptomatic mangabeys carried high viral loads, but macaques generally had higher antibody titers.
- Neutralizing antibodies and antibodies inhibiting reverse transcriptase activity did not correlate with protection in either species.
- Antibodies to an 18-kDa lymphocyte surface protein correlated with disease development, similar to observations in human HIV infection.
Conclusions:
- Antibody responses alone do not appear to prevent SIV/SMM disease progression in macaques or protect mangabeys.
- High viral loads are present even in asymptomatic SIV-infected sooty mangabeys.
- Autoimmune reactions, potentially mediated by antibodies to lymphocyte surface antigens, may contribute to simian AIDS pathogenesis.