A Rhesus Monkey Model for the Study of Bolivian Hemorrhagic Fever

Abstract

Two groups of rhesus monkeys were inoculated with either 10(5) (group 1) or 10(3) (group 2) plaque-forming units of Machupo virus, the etiologic virus of Bolivian hemorrhagic fever. The monkeys were observed for clinical signs; body temperatures, viremias, hematologic changes, and virus-neutralizing antibody were measured. The onset of clinical signs for groups 1 and 2 occurred on days 4-6 and 7-10, respectively, with fever, anorexia, and depression. These and other signs became more severe, and all of the monkeys died; the respective mean times to death for groups 1 and 2 were 14.3 and 19.5 days. Hematocrit, neutrophil, and lymphocyte values decreased in both groups until a few days before death and then increased slightly. Viremias in the two groups peaked on days 13 and 16, respectively, and persisted until death; the sole exception was one monkey in group 2 that developed neutralizing antibody by day 21. The response of the rhesus monkey to Machupo virus thus provides a useful model for the study of Bolivian hemorrhagic fever.

Rescue of a Recombinant Machupo Virus from Cloned cDNAs and In Vivo Characterization in Interferon (αβ/γ) Receptor Double Knockout Mice

“…During the development of this system, we also generated a minigenome (MG) reporter system, which allowed us to study the cis-and trans-acting factors required for MACV replication and gene expression in a BSL-2 environment without select agent restrictions, therefore enhancing our capabilities for potential virus replication studies and drug screening. And finally, we have identified a novel murine model of MACV-induced LNS, similar to what is described in reports of infected humans and NHPs (34)(35)(36). This is the first reported model of LNS in a murine species infected with a New World arenavirus.…”

“…challenge, but the disease development has not been well characterized (9,22). Studies utilizing "chaired" NHPs reported lethal disease development following intradermal, intramuscular, and intranasal challenge (34)(35)(36). Interestingly, African green monkeys, rhesus macaques, and cynomolgus monkeys developed a lethal late neurological syndrome (LNS), a disease also reported in guinea pig models infected with JUNV (37).…”

Pathology of Experimental Machupo Virus Infection, Chicava Strain, in Cynomolgus Macaques (Macaca fascicularis) by Intramuscular and Aerosol Exposure

“…In previous studies, a ''2-phase'' disease was observed in rhesus and cynomolgus macaques challenged subcutaneously with hamster-adapted Caravallo strain of Machupo virus. 9,25,30,40 These studies characterized MACV disease progression in macaques by an initial acute phase beginning at 7 to 10 days postexposure with death occurring generally by the end of week 3. Clinical improvement in survivors of the acute phase occurred around day 21 and progressed for a subsequent 7 to 10 days.…”

Receptor determinants of zoonotic transmission of New World hemorrhagic fever arenaviruses

“…Tyrosine 211 is present in cat TfR1, a very efficient receptor for all three New World hemorrhagic fever arenaviruses. TfR1 from the rhesus macaque, a non-human primate model for MACV and JUNV infections (46,47), also has a tyrosine at position 211. In contrast, position 211 is an aspartic acid in house mouse and rat TfR1 orthologs, preventing efficient arenavirus entry.…”