Immune Response to Marburg Virus Angola Infection in Nonhuman Primates
Lisa Fernando1, Xiangguo Qiu2, P Leno Melito1
1Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada.
Background:
The 2005 outbreak of Marburg virus (MARV) infection in Angola was the most lethal MARV infection outbreak in history, with a case-fatality rate (90%) similar to that for Zaire ebolavirus (EBOV) infection. However, very little is known about the pathogenicity of MARV Angola, as few studies have been conducted to date. Therefore, the immune response was examined in MARV Angola-infected nonhuman primates.
Methods:
Cynomolgus macaques were infected with MARV Angola and monitored for survival. The effect of MARV Angola on the immune system was examined by immunophenotyping whole-blood and by analyzing cytokine and chemokine levels in plasma and spleen specimens, using flow cytometry.
Results:
The prominent clinical findings were rapid onset of disease and death (mean time after infection, 6.7 days), fever, depression, anorexia, petechial rash, and lymphopenia. Specifically, T, B, and natural killer cells were severely depleted in the blood by day 6. The typical cytokine storm was present, with levels of interferon γ, tumor necrosis factor, interleukin 6, and CCL2 rising in the blood early during infection.
Conclusions:
MARV Angola displayed the same virulence and disease pathology as EBOV. MARV Angola appears to cause a more rapid onset and severe outcome of infection than other MARV strains.
Insights
Marburg virus (MARV) Angola infection causes rapid, severe disease and death in nonhuman primates. This study details the immune response, revealing significant cell depletion and a cytokine storm.
Area of Science:
- Virology
- Immunology
- Pathology
Background:
- The 2005 Marburg virus (MARV) Angola outbreak was historically lethal (90% case-fatality rate), comparable to Zaire ebolavirus (EBOV).
- Limited research exists on MARV Angola's pathogenicity, necessitating investigation into its effects on the immune system.
Purpose of the Study:
- To investigate the immune response in nonhuman primates infected with the MARV Angola strain.
- To understand the pathogenicity and clinical outcomes associated with MARV Angola infection.
Main Methods:
- Cynomolgus macaques were experimentally infected with MARV Angola.
- Survival was monitored, and immune responses were assessed via whole-blood immunophenotyping and plasma/spleen cytokine/chemokine analysis using flow cytometry.
Main Results:
- Rapid disease onset and death occurred (mean 6.7 days post-infection), with clinical signs including fever, depression, anorexia, and rash.
- Severe depletion of T cells, B cells, and natural killer cells was observed by day 6.
- A pronounced cytokine storm was evident, characterized by early increases in interferon-γ, tumor necrosis factor, interleukin-6, and CCL2.
Conclusions:
- MARV Angola exhibits virulence and pathology similar to EBOV.
- MARV Angola infection appears to result in a more rapid and severe outcome compared to other MARV strains.
