Temporal analysis of Lassa virus infection and transmission in experimentally infected Mastomys natalensis

Abstract

Little is known about the temporal patterns of infection and transmission of Lassa virus (LASV) within its natural reservoir (Mastomys natalensis). Here we characterize infection dynamics and transmissibility of a LASV isolate (Soromba-R) in adult lab-reared M. natalensis originating from Mali. The lab-reared M. natalenesis proved to be highly susceptible to LASV isolates from geographically distinct regions of West Africa via multiple routes of exposure, with 50% infectious doses of < 1 TCID50. Post-inoculation, LASV Soromba-R established a systemic infection with no signs of clinical disease. Viral RNA was detected in all nine tissues examined with peak concentrations detected between days 7 and 14 post-infection within most organs. There was an overall trend towards clearance of virus within 40 days of infection in most organs. The exception is lung specimens, which retained positivity throughout the course of the 85-day study. Direct (contact) and indirect (fomite) transmission experiments demonstrated 40% of experimentally infected M. natalensis were capable of transmitting LASV to naïve animals, with peak transmissibility occurring between 28 and 42 days post-inoculation. No differences in patterns of infection or transmission were noted between male and female experimentally infected rodents. Adult lab-reared M. natalensis are highly susceptible to genetically distinct LASV strains developing a temporary asymptomatic infection associated with virus shedding resulting in contact and fomite transmission within a cohort.

Lassa virus persistence with high viral titers following experimental infection in its natural reservoir host, Mastomys natalensis

“…Detailed analysis of H&E-stained tissue samples showed that none of the investigated organs displayed signs of immune in ltration, cell loss, or degeneration, despite a sometimes very high viral load. This lack of apparent pathology re ects descriptions from previous studies with LASV and the closely related MORV [26][27][28][29] , and is also in concordance with observations from LASV-infected M. natalensis in the wild 46 . Effective virus control in transiently infected animals has previously been associated with short-lived alterations of clinical analytes and histological abnormalities in several organs, such as immune cell in ltrations, interstitial thickening, or tissue disruption in otherwise subclinical animals 26 .…”

“…Inoculated two-week-old animals no longer developed stable persistent infections, but instead cleared the virus, albeit protracted over the course of several weeks. Animals aged four weeks and older only developed very short-lived transient infections, matching observations made in other studies 26,27 .…”

“…Upon inoculation with LASV, adult Mastomys developed systemic but subclinical infections with detectable viral RNA in blood, urine and various tissues. However, the authors could only observe transient infections, characterized by brief periods of detectable viremia, while viral RNA in organs remained detectable for several weeks 26,27 . Persistent LASV infection on the other hand has so far only been reported once for a small number of animals.…”

The Importance of Lassa Fever and Its Disease Management in West Africa

“…Lassa virus (LASV) is the zoonotic pathogen responsible for causing Lassa fever (LF), a potentially hemorrhagic human disease endemic throughout western Africa [ 1 ]. This Old-World arenavirus predominately infects Mastomys natalensis as its major reservoir host, although recent work has identified LASV within Hylomyscus pamfi and M. erythroleucus rodents as well, with the virus shedding into their urine and feces [ 2 , 3 , 4 , 5 , 6 ]. The synanthropic nature of this rodent species, combined with its ability to shed the virus continuously, is highly conducive to LASV spillover into human populations [ 7 ].…”

Novel Tools for Lassa Virus Surveillance in Peri-domestic Rodents

“…infected with mammarenaviruses as adults, on the other hand, rapidly clear the virus and develop high levels of antiviral antibodies. 18,19 Understanding the link between concurrent antigen and antibody presence could also help to further elucidate the ecological niches permissive to LASV infection.…”