Experimental Studies of Arenaviral Hemorrhagic Fevers

Circulating natural killer and γδ T cells decrease soon after infection of rhesus macaques with lymphocytic choriomeningitis virus

“…Every year, Lassa fever and the South American hemorrhagic fever viruses account for almost half a million cases worldwide, with approximately 16% mortality (Jahrling et al 1985, McCormick et al 1986, Fisher-Hoch et al 2000. Although rodents serve as a reservoir for arenaviruses, studies of hemorrhagic fever have relied on guinea pig, hamster and primate models rather than mouse models because the disease mechanism is fundamentally different in non-reservoir species (Peters et al 1987).…”

“…Every year, Lassa fever and the South American hemorrhagic fever viruses account for almost half a million cases worldwide, with approximately 16% mortality (Jahrling et al 1985, McCormick et al 1986, Fisher-Hoch et al 2000. Although rodents serve as a reservoir for arenaviruses, studies of hemorrhagic fever have relied on guinea pig, hamster and primate models rather than mouse models because the disease mechanism is fundamentally different in non-reservoir species (Peters et al 1987).Numerous murine studies of viral persistence and cell-mediated immunity have involved the prototype arenavirus, lymphocytic choriomeningitis virus (LCMV) , Ahmed et al 1984, Salvato et al 1991. The WE strain of LCMV is hepatotropic in mice, guinea pigs and primates (Riviere et al 1985, Zinkernagel et al 1986, Lukashevich et al 2002, but in contrast to murine LCMV infections, LCMV-WE infection of rhesus macaques can resemble Lassa hemorrhagic fever in human beings (Jahrling et al 1980, Peters et al 1987, Lukashevich et al 2002.…”

“…Although rodents serve as a reservoir for arenaviruses, studies of hemorrhagic fever have relied on guinea pig, hamster and primate models rather than mouse models because the disease mechanism is fundamentally different in non-reservoir species (Peters et al 1987).…”

“…The WE strain of LCMV is hepatotropic in mice, guinea pigs and primates (Riviere et al 1985, Zinkernagel et al 1986, Lukashevich et al 2002, but in contrast to murine LCMV infections, LCMV-WE infection of rhesus macaques can resemble Lassa hemorrhagic fever in human beings (Jahrling et al 1980, Peters et al 1987, Lukashevich et al 2002. The Armstrong (ARM) strain of LCMV does not cause overt disease in monkeys, even after intravenous inoculation (Danes et al 1963, Peters et al 1987, Lukashevich et al 2002.Several immunological studies have shown the importance of CD8 T lymphocytes in both protection and in induction of immuno-pathogenesis in the mouse model , Bonilla et al 2002. More recently, we demonstrated the importance of cell-mediated immunity in survival after a lethal intravenous challenge in the primate model .…”

“…Although our study failed to show a significant difference between the benign and virulent infections, it is possible that a study with more time points could detect kinetic differences in NK loss differentiating these two infections. Since ARM-infection immunises monkeys from lethal LCMV-WE challenge (Danes et al 1963, Peters et al 1987, it is notable that a drop in NK cells is seen during a WE challenge infection in the absence of pathogenesis.Murine infections with LCMV have provided a large body of information on innate immune responses after viral inoculation. Interferon type I (or IFN α/β) is produced by infected cells soon after LCMV infection of the mouse and it then activates NK cells to proliferate and carry out their cytotoxic role (Biron et al 1996.…”