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CD4+-T-cell and CD20+-B-cell changes predict rapid disease progression after simian-human immunodeficiency virus
K K Steger1, M Dykhuizen, J L Mitchen
1Department of Pathology and Laboratory Medicine, University of Wisconsin Medical School, Madison 53706, USA.
Abstract:
Simian-human immunodeficiency virus 89.6PD (SHIV89.6PD) was pathogenic after intrarectal inoculation of rhesus macaques. Infection was achieved with a minimum of 2,500 tissue culture infectious doses of cell-free virus stock, and there was no evidence for transient viremia in animals receiving subinfectious doses by the intrarectal route. Some animals experienced rapid progression of disease characterized by loss of greater than 90% of circulating CD4+ T cells, sustained decreases in CD20+ B cells, failure to elicit virus-binding antibodies in plasma, and high levels of antigenemia. Slower-progressing animals had moderate but varying losses of CD4+ T cells; showed increases in circulating CD20+ B cells; mounted vigorous responses to antibodies in plasma, including neutralizing antibodies; and had low or undetectable levels of antigenemia. Rapid progression led to death within 30 weeks after intrarectal inoculation. Plasma antigenemia at 2 weeks after inoculation (P < or = 0.002), B- and T-cell losses (P < or = 0.013), and failure to seroconvert (P < or = 0.005) were correlated statistically with rapid progression. Correlations were evident by 2 to 4 weeks after intrarectal SHIV inoculation, indicating that early events in the host-pathogen interaction determined the clinical outcome.
Insights
Simian-human immunodeficiency virus (SHIV) infection in macaques can rapidly progress to severe disease. Early indicators like antigenemia and immune cell loss predict rapid progression and poor outcomes.
Area of Science:
- Virology
- Immunology
- Primate Models
Background:
- Simian-human immunodeficiency virus (SHIV) is a primate model for HIV research.
- Intrarectal inoculation is a relevant route for studying viral transmission and pathogenesis.
Purpose of the Study:
- To investigate the pathogenesis of SHIV89.6PD after intrarectal inoculation in rhesus macaques.
- To identify early predictors of rapid disease progression.
Main Methods:
- Rhesus macaques were intrarectally inoculated with varying doses of SHIV89.6PD.
- Viral load, CD4+ T cell counts, CD20+ B cell counts, antibody responses, and antigenemia were monitored.
- Statistical correlations between early events and disease progression were analyzed.
Main Results:
- SHIV89.6PD infection was pathogenic, with rapid progression observed in some macaques.
- Rapid progression was characterized by severe CD4+ T cell loss, decreased B cells, lack of antibody response, and high antigenemia.
- Slower progression showed moderate CD4+ T cell loss, increased B cells, robust antibody responses, and low antigenemia.
- Early plasma antigenemia, immune cell loss, and failure to seroconvert at 2-4 weeks post-inoculation predicted rapid disease progression and mortality within 30 weeks.
Conclusions:
- Early host-pathogen interactions following intrarectal SHIV inoculation determine clinical outcomes.
- Plasma antigenemia, immune cell dynamics, and seroconversion status are critical early predictors of SHIV disease progression.