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

Abstract

bRabies virus (RABV) maintenance in bats is not well understood. Big brown bats (Eptesicus fuscus), little brown bats (Myotis lucifugus), and Mexican free-tailed bats (Tadarida brasiliensis) are the most common bats species in the United States. These colonial bat species also have the most frequent contact with humans and domestic animals. However, the silver-haired bat (Lasionycteris noctivagans) RABV is associated with the majority of human rabies virus infections in the United States and Canada. This is of interest because silver-haired bats are more solitary bats with infrequent human interaction. Our goal was to determine the likelihood of a colonial bat species becoming infected with and transmitting a heterologous RABV. To ascertain the potential of heterologous RABV infection in colonial bat species, little brown bats were inoculated with a homologous RABV or one of two heterologous RABVs. Additionally, to determine if the route of exposure influenced the disease process, bats were inoculated either intramuscularly (i.m.) or subcutaneously (s.c.) with a homologous or heterologous RABV. Our results demonstrate that intramuscular inoculation results in a more rapid progression of disease onset, whereas the incubation time in bats inoculated s.c. is significantly longer. Additionally, cross protection was not consistently achieved in bats previously inoculated with a heterologous RABV following a challenge with a homologous RABV 6 months later. Finally, bats that developed rabies following s.c. inoculation were significantly more likely to shed virus in their saliva and demonstrated increased viral dissemination. In summary, bats inoculated via the s.c. route are more likely to shed virus, thus increasing the likelihood of transmission. Lyssavirus infections have been reported in numerous species of terrestrial and flying mammals (1, 2). Several regions of enzootic rabies virus (RABV) activity occur in raccoon, skunk, and fox populations within the continental United States. These enzootic foci are generally limited to homologous infections; e.g., raccoons are infected with a raccoon rabies virus variant (2). Despite less geographical isolation, chiropteran RABVs are also typically limited to their host species (3). However, RABV spillover into heterologous hosts does occur and has been implicated in the origin of raccoon-and skunk-adapted RABVs (4).Two of the most common species of bats in the continental Unites States are the big brown bat (Eptesicus fuscus) and the little brown bat (Myotis lucifugus) (5). These highly colonial species are adapted to living in both urban and rural areas. On the basis of data from public health rabies laboratories, big brown bats and little brown bats are the bat species most commonly submitted for rabies testing. The large number of submissions stems from human or domestic animal exposure (6). Despite frequent interaction, only three human rabies cases acquired in the United States have been associated with the little brown bat or big brown bat RABV since 1990 (Fox News)...

Chiroptera

“…In one study of bats infected with Australian bat lyssavirus, the highest frequency and severity of microscopic lesions was detected in the hippocampus, thalamus and midbrain, and medulla oblongata and pons (Hooper et al, 1999). Lyssaviral antigen has been detected in bats in the central and peripheral nervous system as well as in other tissues; reported affected sites include brainstem, cerebellar Purkinje cells, hippocampus, cerebrum, thalamus and midbrain, peripheral autonomic ganglia, nerve plexuses of the gastrointestinal tract, intramuscular nervous tissue, adrenal medulla, salivary gland, tongue, brown fat, lung, heart, kidney, bladder, stomach, intestine, and feces (Allendorf et al, 2012;Davis et al, 2013;de Araújo et al, 2014;Hooper et al, 1999;Schatz et al, 2014;Stein et al, 2010).…”

Detection of rabies virus in organs unrelated to the central nervous system of experimentally-inoculated vampire bats

“…Some reports (18) , detected RABV in saliva in surviving individuals at 6 and 21 d by cell culture, while in this study MIT was used, which is a historical test for isolation and at least as sensitive as cell culture. Davis et al (11) were unable to detect RABV in saliva of the insectivorous bat Myotis lucifugus subcutaneously inoculated. Other work (9) , detected RABV in only 10 % of E. fuscus, which had been inoculated IM with a homologous RABV, although positive samples were detected before the onset of disease and none of the survivors showed viral excretion.…”

“…Specific viral detection in rabid bats varies by species and the particular methods used in regards to dose and route. For example, some researchers (11) detected a fragment of RABV in insectivorous bats only in salivary glands and nervous tissue, but they also reported differing results using PCR and isolation with these same tissues. In the present study, it was not possible to detect RABV in saliva either by molecular tools or biological tests, which could be related to the inoculation pathway used.…”

“…Recently, several studies have been published in Europe and North America concerning experimental inoculation of insectivorous bats, using homologous RABV (9,10,11) , Irkut virus (IRKV) (12) as well as heterologous viruses (European bat lyssavirus 1 (EBL-1) and European bat lyssavirus 1 (EBL-2) (11)(12)(13)(14)(15)(16) . By comparison, only a few studies have been conducted on hematophagous bats (17)(18)(19)(20) , in an attempt to understand the transmission and perpetuation of RABV in wild populations of D. rotundus.…”

Rabies surveillance in wild mammals in South of Brazil

“…Strain‐level differences among RABV variants, for instance, affect the outcome of the exposure. For example, infections in heterologous hosts show altered patterns of infectivity and pathogenesis and could result in abortive/highly lethal infections that would be expected to limit onward transmission (Davis, Jarvis, Pouliott, Morgan, & Rudd, ; Hamir, Moser, & Rupprecht, ). Possibly, these factors contribute to the absence of rabid wild animals in south of Brazil so far, despite the RVNA positivity described here and the endemic situation of wild rabies in bats.…”