Abstract
Rift Valley fever virus (RVFV) leads to varied clinical manifestations in animals and in humans that range from moderate fever to fatal illness, suggesting that host immune responses are important determinants of the disease severity. We investigated the immune basis for the extreme susceptibility of MBT/Pas mice that die with mild to acute hepatitis by day 3 post-infection compared to more resistant BALB/cByJ mice that survive up to a week longer. Lower levels of neutrophils observed in the bone marrow and blood of infected MBT/Pas mice are unlikely to be causative of increased RVFV susceptibility as constitutive neutropenia in specific mutant mice did not change survival outcome. However, whereas MBT/Pas mice mounted an earlier inflammatory response accompanied by higher amounts of interferon (IFN)-α in the serum compared to BALB/cByJ mice, they failed to prevent high viral antigen load. Several immunological alterations were uncovered in infected MBT/Pas mice compared to BALB/cByJ mice, including low levels of leukocytes that expressed type I IFN receptor subunit 1 (IFNAR1) in the blood, spleen and liver, delayed leukocyte activation and decreased percentage of IFN-γ-producing leukocytes in the blood. These observations are consistent with the complex mode of inheritance of RVFV susceptibility in genetic studies.
Highlights
To cite this version: Rashida Lathan, Dominique Simon-Chazottes, Grégory Jouvion, Ophélie Godon, Marie Malissen, et al
We have previously shown that wild-derived inbred MBT/Pas (MBT) mice are highly susceptible to infection with the virulent Rift Valley fever virus (RVFV) ZH548 and Kenya 98 strains in comparison to more resistant BALB/cByJ (BALB/c) mice[11]
BALB/c mice died at a median of 8 days, and 3 out of 28 (11%) survived past 12 days post infection with 100 plaque-forming units (PFU) of RVFV strain ZH548
Summary
To cite this version: Rashida Lathan, Dominique Simon-Chazottes, Grégory Jouvion, Ophélie Godon, Marie Malissen, et al. We assessed levels of RVFV nucleoprotein (N) antigen in single-cell suspensions of the brain, blood, spleen, and liver from BALB/c and MBT mice on days 1–3 post RVFV infection using flow cytometric analysis. The average percentages of viral antigen-positive cells were significantly higher on days 2 and 3 post infection in MBT mice compared to BALB/c mice (Fig. 3a).
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