Lassa Virus Infection in Experimentally Infected Marmosets: Liver Pathology and Immunophenotypic Alterations in Target Tissues

Abstract

Lassa virus causes thousands of deaths annually in western

Pathogenic Old World Arenaviruses Inhibit TLR2/Mal-Dependent Proinflammatory Cytokines In Vitro

“…In contrast, in good correlation with our results, in progressed LF patients, fatal infection was correlated with low or undetectable levels of proinflammatory cytokines/chemokines, including IL-8 and IP-10 (39). At present, the immunosuppressive phenotype of progressed LASV infection in humans or in nonhuman primates is a well-accepted concept (7,15,46,49,62). Our previously reported gene expression analysis of human peripheral blood mononuclear cells (PBMC) from healthy donors exposed to LASV has shown that IFN-related genes and genes involved in apoptosis, NF-B, and coagulation pathways were among the genes most affected by LASV (61).…”

“…In contrast to filovirus VHF (23), in LF patients, the profound shock, vascular damage, and hemorrhage in late-stage victims of Old World arenaviruses are not associated with a "cytokine storm." In fact, we (15,35,38) and others (5-7, 27, 39, 40) showed that LASV replication in vitro and in vivo is associated with the suppression of proinflammatory responses, impaired activation of innate immune cells, and delayed cytotoxic T cell responses, contributing to unchecked viremia and fatal outcomes.…”

Vaccines against viral hemorrhagic fevers: Non-human primate models

“…18 As with the macaque model, experimental infection of common marmosets with LASV (Josiah strain) results in a systemic viral disease with high viremia and high viral RNA load in tissues and elevated liver enzymes. 18,19 Morphologic features mimic those described in human cases of fatal LF, and include hepatic and adrenal necrosis, lymphoid depletion and interstitial nephritis.…”

“…2,61 Experimental ZEBOV infection of macaques by intramuscular injection of 1,000 PFU of virus results in a rapid, fatal disease. 14,18,19 Beginning at day 4 post-infection, macaques experienced anorexia coinciding with the onset of fever. Shortly after these initial findings, petechial rash ( Fig.…”

“…Examination of spleen tissue reveals reduction in overall numbers of CD3 -and CD20 + lymphocytes in infected marmosets. 18,19 Previously published evidence for immunosuppression by LASV infection was primarily based on in vitro data [21][22][23][24] and proinflammatory cytokine profiles in plasma of experimentally infected animals, 23 or in Lassa fever patients. 25 The marmoset model of LF has provided the first experimental evidence that replication of Lassa virus in target tissues of is associated with alterations that would be expected to impare adaptive immunity.…”