Experimental Morogoro Virus Infection in Its Natural Host, Mastomys natalensis

Abstract

Natural hosts of most arenaviruses are rodents. The human-pathogenic Lassa virus and several non-pathogenic arenaviruses such as Morogoro virus (MORV) share the same host species, namely Mastomys natalensis (M. natalensis). In this study, we investigated the history of infection and virus transmission within the natural host population. To this end, we infected M. natalensis at different ages with MORV and measured the health status of the animals, virus load in blood and organs, the development of virus-specific antibodies, and the ability of the infected individuals to transmit the virus. To explore the impact of the lack of evolutionary virus–host adaptation, experiments were also conducted with Mobala virus (MOBV), which does not share M. natalensis as a natural host. Animals infected with MORV up to two weeks after birth developed persistent infection, seroconverted and were able to transmit the virus horizontally. Animals older than two weeks at the time of infection rapidly cleared the virus. In contrast, MOBV-infected neonates neither developed persistent infection nor were able to transmit the virus. In conclusion, we demonstrate that MORV is able to develop persistent infection in its natural host, but only after inoculation shortly after birth. A related arenavirus that is not evolutionarily adapted to M. natalensis is not able to establish persistent infection. Persistently infected animals appear to be important to maintain virus transmission within the host population.

Inoculation route-dependent Lassa virus dissemination and shedding dynamics in the natural reservoir – Mastomys natalensis

“…The age of the animals at the time of infection should be emphasized. It has been repeatedly shown that M. natalensis and other rodents that are infected with arenaviruses in utero , perinatally or in neonatal stages postpartum, remain persistently infected and shed virus in urine for long periods [ 23–26 ], which also holds true for LASV, as preliminary studies demonstrated [ 14 ]. Likewise, heterologous LASV infection in neonatal M. musculus resulted in prolonged shedding in the urine [ 44 ].…”

“…Therefore, persistent infection and shedding after vertical transmission or early postpartum infection is a plausible mode of maintenance of LASV in wild populations of M. natalensis and remains a potential source of rodent-to-human transmission. For the LASV-related Morogoro virus, horizontal transmission to neonates of M. natalensis from persistently infected individuals reduced the chance of persistent infection with this LASV-related arenavirus by 20–60% compared to s.c.-inoculation at day two after birth [ 23 ]. Likewise, the inoculation route might be a major factor in LASV persistence and needs to be thoroughly considered if experimental data are to be applied to virus transmission in a wild population.…”

“…A minority of LF cases stem from human-to-human transmissions in nosocomial settings, and though these outbreaks garner much attention [ 1 , 21 ], the vast majority of human infections are zoonotic, demonstrated by LASV genome sequencing during spill-over [ 22 ]. Transmission within M. natalensis populations likely occurs in utero and during perinatal contact, deduced from preliminary studies on M. natalensis and other arenaviruses in their natural reservoirs [ 14 , 23–26 ], however, infection of naïve adult animals and the virus dynamics in M. natalensis have not been sufficiently researched. Human spill-over is generally thought to occur by contamination of foodstuffs and surfaces with LASV-contaminated faeces or urine of M. natalensis [ 27 ] but has not been definitively determined.…”

Common Themes in Zoonotic Spillover and Disease Emergence: Lessons Learned from Bat- and Rodent-Borne RNA Viruses

“…However, persistent infection as a mechanism of maintenance in the reservoir population may depend on the age of infection. For arenaviruses such as Guanarito mammarenavirus , JUNV, LASV, LCMV, MACV, and Morogoro virus, studies have shown an age-dependency in the duration of infection among reservoir hosts [ 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 ]. Neonates develop long-term viral persistence, while adults can clear infection [ 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 ].…”

“…For arenaviruses such as Guanarito mammarenavirus , JUNV, LASV, LCMV, MACV, and Morogoro virus, studies have shown an age-dependency in the duration of infection among reservoir hosts [ 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 ]. Neonates develop long-term viral persistence, while adults can clear infection [ 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 ]. The mechanism by which virus persists or is cleared is an area in need of additional investigation.…”