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Interactions between Mycobacterium leprae and simian immunodeficiency virus (SIV) in rhesus monkeys
B J Gormus1, M Murphey-Corb, G B Baskin
1Department of Microbiology, Tulane University Regional Primate Research Center, Covington, LA 70433, USA. gormus@tpc.tulane.edu
Abstract:
Groups of rhesus monkeys were inoculated with: 1) simian immunodeficiency virus (SIV)B670 alone; 2) Mycobacterium leprae alone; 3) SIV plus M. leprae on the same day; and 4) M. leprae 2 weeks after SIV. Animals were monitored at intervals for virus loads, antibody responses to M. leprae glycolipid antigens and to SIV Gp120, T-cell CD4+ and CD4+ CD29+ subset percentages, leprosy and acquired immunodeficiency syndrome (AIDS) clinical symptoms. Five out of six animals developed leprosy in each co-inoculated group, compared to one out of six in the M. leprae-only-inoculated group, indicating that M. leprae/SIV co-infection increases the susceptibility to leprosy, regardless of the timing of the two infections. Animals in the co-infected group that received M. leprae 2 weeks after SIV had a significantly slower rate of AIDS progression and long-term survival was significantly greater (three out of six) compared to the group inoculated with SIV alone (zero out of seven). All M. leprae-only-inoculated animals (six out of six) survived. Post-SIV-inoculation, a rapid decrease in the percentages of CD4 + and CD4 + CD29 + T-cells was observed in the SIV-only-inoculated group that was significantly blocked by co-inoculation with M. leprae 2 weeks after SIV, but not by SIV on the same day. The virus load set point was increased by approximately two logs in the group inoculated with M. leprae and SIV on the same day compared to SIV 2 weeks prior to M. leprae or the SIV-only-inoculated group. The results indicate that M. leprae, inoculated 2 weeks after SIV, decreased the pathogenicity of SIV compared to inoculation of M. leprae and SIV on the same day or SIV alone. The decreased pathogenicity correlated with a diminished loss of CD4 + and CD4 + CD29 + T-cell subsets in the group inoculated with M. leprae 2 weeks after SIV compared to the group inoculated with SIV alone. IgG antibody responses to M. leprae-specific cell wall phenolic glycolipid-I antigen were inhibited by 2-week-prior or same-day SIV co-inoculation compared to M. leprae-only inoculated animals. The IgG anti-lipoarabinomannan antibody response was enhanced in the group inoculated with M. leprae and SIV on the same day compared to the groups inoculated with M. leprae alone or SIV 2 weeks prior to M. leprae. Antibody responses to SIV Gp120 antigen were unimpaired in both co-inoculated groups compared to SIV-only-inoculated groups. The antibody results show that the immune responses to SIV and M. leprae are interrelated in SIV/M. leprae co-infected animals.
Insights
Co-infection with Mycobacterium leprae (M. leprae) and simian immunodeficiency virus (SIV) increases leprosy susceptibility. However, M. leprae administered 2 weeks after SIV in rhesus monkeys significantly slowed AIDS progression and improved survival.
Area of Science:
- Immunology
- Virology
- Infectious Diseases
Background:
- Simian immunodeficiency virus (SIV) causes an AIDS-like illness in rhesus monkeys.
- Mycobacterium leprae (M. leprae) causes leprosy, a chronic infectious disease.
- The interaction between SIV and M. leprae co-infections is not well understood.
Purpose of the Study:
- To investigate the impact of M. leprae and SIV co-infection on disease progression and immune responses in rhesus monkeys.
- To determine if the timing of M. leprae and SIV inoculation affects disease outcomes.
Main Methods:
- Rhesus monkeys were inoculated with SIV alone, M. leprae alone, or co-infected with SIV and M. leprae at different time points.
- Animals were monitored for viral loads, antibody responses (to M. leprae and SIV antigens), T-cell subset percentages (CD4+ and CD4+CD29+), and clinical symptoms of leprosy and AIDS.
- Statistical analyses were performed to compare outcomes between different inoculation groups.
Main Results:
- Co-infection with M. leprae and SIV increased susceptibility to leprosy compared to M. leprae alone.
- M. leprae administered 2 weeks after SIV significantly slowed AIDS progression and increased long-term survival compared to SIV alone.
- M. leprae co-infection modulated T-cell dynamics and viral load set points, with timing influencing the outcome.
Conclusions:
- M. leprae co-infection exacerbates leprosy but can decrease SIV pathogenicity when administered 2 weeks after SIV.
- The timing of M. leprae and SIV co-infection significantly impacts SIV disease progression and host immune responses.
- Immune responses to SIV and M. leprae are interrelated in co-infected animals.