Host immunity to repeated rabies virus infection in big brown bats

Abstract

Bats are natural reservoirs for the majority of lyssaviruses globally, and are unique among mammals in having exceptional sociality and longevity. Given these facets, and the recognized status of bats as reservoirs for rabies viruses (RABVs) in the Americas, individual bats may experience repeated exposure to RABV during their lifetime. Nevertheless, little information exists with regard to within-host infection dynamics and the role of immunological memory that may result from abortive RABV infection in bats. In this study, a cohort of big brown bats (Eptesicus fuscus) was infected intramuscularly in the left and right masseter muscles with varying doses [10−0.1–104.9 median mouse intracerebral lethal doses (MICLD50)] of an E. fuscus RABV variant isolated from a naturally infected big brown bat. Surviving bats were infected a second time at 175 days post-(primary) infection with a dose (103.9–104.9 MICLD50) of the same RABV variant. Surviving bats were infected a third time at either 175 or 305 days post-(secondary) infection with a dose (104.9 MICLD50) of the same RABV variant. When correcting for dose, similar mortality was observed following primary and secondary infection, but reduced mortality was observed following the third and last RABV challenge, despite infection with a high viral dose. Inducible RABV-neutralizing antibody titres post-infection were ephemeral among infected individuals, and dropped below levels of detection in several bats between subsequent infections. These results suggest that long-term repeated infection of bats may confer significant immunological memory and reduced susceptibility to RABV infection.

Susceptibility and Pathogenesis of Little Brown Bats (Myotis lucifugus) to Heterologous and Homologous Rabies Viruses

“…Although i.m. inoculation is believed to be the most common route of RABV transmission between terrestrial mammals, it may be different among chiropterans (17,18) On the basis of our data, i.m. inoculation is more likely to result in clinical infection yet is less likely to result in dissemination of the virus to the salivary glands.…”

“…challenge (20). Clinical RABV infection is more likely following inoculation with higher viral titers (17,21). Indeed, the route to clinical RABV infection is multifactorial.…”

“…RABV challenge, previous i.m. and s.c. exposure may provide some level of protection against future RABV exposures (17,21).…”

Bat Reservoirs for Rabies Virus and Epidemiology of Rabies in Colombia: a review

“…These animals are unique among mammals due to having exceptional sociality and longevity. Given these features and the recognized status of bats as reservoirs for RABVs in the Americas, individual bats may experience repeated exposure to RABV during their lifetime 22 . Hematophagous, frugivorous, and insectivorous bats can transmit http://dx.doi.org/10.21615/cesmvz.12.2.5 the RABV 23 , and phylogenetic analysis using nucleotide sequences of N or G genes revealed that RABV is grouped into clusters according to the bat species that support the existence of species-specific variants or lineages of the virus 19,24 .…”

The interplay between viruses and the immune system of bats

“…Over the past few years, considerable headway has been made into elucidating the mechanisms responsible for the ability of bats to control viral replication, with evidence for unique differences in the innate immune responses of bats [14][15][16][17][18][19][20] . However, many However, evidence from experimental infections have shown the development of neutralising antibodies is often delayed and some animals fail to generate an antibody response within the timeframe of the experiment 8,11,12,27,28 . This coupled with the constitutive activation of components of the innate immune system may mean that the adaptive immune response in bats is less critical.…”