Experimental Infection of Rhesus Monkeys with Lassa Virus and a Closely Related Arenavirus, Mozambique Virus

Abstract

As a model for the pathogenesis of Lassa fever in humans, nine rhesus monkeys were inoculated with Lassa virus. Three monkeys had had a previous asymptomatic experimental infection with Mozambique virus, a closely related arenavirus; these monkeys were protected from illness and viremia and manifested only mild pathologic lesions. The other animals developed severe disease and viremia. At necropsy, hepatocellular necrosis, interstitial pneumonia, a unique pulmonary arteritis, adrenal gland necrosis, encephalitis, and uveitis were prominent pathologic lesions which correlated with the organ titers of virus. One animal infected with Lassa virus developed prolonged viremia, a typical immune response, and sudden onset of lower limb paralysis after recovery; at necropsy chronic proliferative arteritis of the spinal cord, brain, and heart was evident. Similarities and differences in the pathologic lesions in this model and Lassa fever in humans indicate that care must be taken in interpreting the results of experiments concerning immune prophylaxis, pathogenesis, and treatment in rhesus monkeys.

Early and Strong Immune Responses Are Associated with Control of Viral Replication and Recovery in Lassa Virus-Infected Cynomolgus Monkeys

“…Although we had to euthanize one animal for ethical reasons before he succumbed to the disease, we could reasonably assume that this animal would not have recovered from the disease. Indeed, hypothermia, respiratory syndrome, and neurological signs are characteristic of the terminal stages of Lassa fever (7,65). Furthermore, similar levels of biological markers were detected in this animal and the monkey that succumbed to the disease, with elevated AST/ALT levels, uncontrolled viremia, and high levels of plasmatic IL-6 at the end of the disease.…”

“…Here, we report some virological, pathological, and immunological variables associated with fatal and nonfatal outcomes after LV infection of cynomolgus monkeys. Both rhesus monkeys (7,26,33,65) and cynomolgus monkeys have frequently been used as models for Lassa fever, and similar clinical signs and pathological events have been observed after LV infection in these closely related species (16,21,27,29,58). We used two different doses of virus to assess the influence of the viral inoculum on the disease course, and because the AV strain of LV has never been evaluated in primate models.…”

“…Therefore, nonhuman primates are still the only relevant model for Lassa fever: rhesus and cynomolgus monkeys (Macaca mulatta and Macaca fascicularis, respectively) are the primates that have been most extensively used (7,16,21,26,27,29,58,65). These closely related nonhuman primates both reproduce the systemic disease involving most of the visceral organs, with microscopic lesions, including hepatocellular necrosis, interstitial pneumonia, arteritis, and encephalitis.…”

Vaccines against viral hemorrhagic fevers: Non-human primate models

“…Necrosis of liver, adrenal and spleen is a prominent feature of LASV infection in rhesus macaques. [13][14][15][16][17] This model has been used to show efficacy of ribavirin in treatment of LF. 15 The common marmoset (Callithrix jacchus), a small anthropoid NHP, has also been shown to mirror human LF.…”

Molecular characterization of a reassortant virus derived from Lassa and Mopeia viruses

“…It is carried by the African multi-mammate rat, Mastomys natalensis, widely spread in sub-Saharan Africa [3]. In contrast to its West African relative, LAS virus, MOP virus causes no lethal disease in guinea pigs or primates and can be used to vaccinate against LAS virus [4]. the replication machinery of MOP and the antigenic determinants of LAS virus was chosen for further characterization as a potential vaccine.…”