Experimental Lagos bat virus infection in straw-colored fruit bats: A suitable model for bat rabies in a natural reservoir species

Abstract

Rabies is a fatal neurologic disease caused by lyssavirus infection. Bats are important natural reservoir hosts of various lyssaviruses that can be transmitted to people. The epidemiology and pathogenesis of rabies in bats are poorly understood, making it difficult to prevent zoonotic transmission. To further our understanding of lyssavirus pathogenesis in a natural bat host, an experimental model using straw-colored fruit bats (Eidolon helvum) and Lagos bat virus, an endemic lyssavirus in this species, was developed. To determine the lowest viral dose resulting in 100% productive infection, bats in five groups (four bats per group) were inoculated intramuscularly with one of five doses, ranging from 100.1 to 104.1 median tissue culture infectious dose (TCID50). More bats died due to the development of rabies after the middle dose (102.1 TCID50, 4/4 bats) than after lower (101.1, 2/4; 101.1, 2/4) or higher (103.1, 2/4; 104.1, 2/4) doses of virus. In the two highest dose groups, 4/8 bats developed rabies. Of those bats that remained healthy 3/4 bats seroconverted, suggesting that high antigen loads can trigger a strong immune response that abrogates a productive infection. In contrast, in the two lowest dose groups, 3/8 bats developed rabies, 1/8 remained healthy and seroconverted and 4/8 bats remained healthy and did not seroconvert, suggesting these doses are too low to reliably induce infection. The main lesion in all clinically affected bats was meningoencephalitis associated with lyssavirus-positive neurons. Lyssavirus antigen was detected in tongue epithelium (5/11 infected bats) rather than in salivary gland epithelium (0/11), suggesting viral excretion via the tongue. Thus, intramuscular inoculation of 102.1 TCID50 of Lagos bat virus into straw-colored fruit bats is a suitable model for lyssavirus associated bat rabies in a natural reservoir host, and can help with the investigation of lyssavirus infection dynamics in bats.

Lagos Bat Virus, an Under-Reported Rabies-Related Lyssavirus

“…Experimental infections (Table 6) have mostly been performed in non-reservoir hosts, such as mice, potentially resulting in inaccurate disease progression assumptions in naturally infected animals. More recently, the pathogenesis of LBV in one of its natural hosts, i.e., E. helvum, was investigated [63,64]. Similar mortality rates, as observed in other animals, were reported (Table 6).…”

“…The mechanisms of virus maintenance and transmission of lyssaviruses in bats are not well understood and could be influenced by various factors [2,26]. The experimental infection of E. helvum with LBV indicated that bats that survived the challenge had developed virus neutralizing antibodies (53%), suggesting that bats can develop an immune response without clinical disease development and thus not excrete virus [63]. This would support surveillance results, indicating high seroprevalence and low virus detection in Africa.…”

“…Additionally, lyssavirus antigens were detected in tongue epithelium and, together with the salivary glands, are probable virus excretion sites [63,64]. However, it was noted that for four bats, experimentally infected with different LBV doses (10 0.1 -10 4.1 TCID 50 ), no clinical signs were observed before the bats were found dead [63]. This phenomenon has also been reported in bats naturally infected with LBV and warrants further investigation [1,11].…”

“…Clinical signs observed in experimentally infected bats appear similar to animals naturally infected with LBV (Figure 5). Additionally, lyssavirus antigens were detected in tongue epithelium and, together with the salivary glands, are probable virus excretion sites [63,64]. However, it was noted that for four bats, experimentally infected with different LBV doses (10 0.1 -10 4.1 TCID 50 ), no clinical signs were observed before the bats were found dead [63].…”

“…Protection against disease development following exposure is reliant on both the innate (i.e., the basic immune system that induces non-specific resistance to disease) and the adaptive immune responses (i.e., highly specialized and systemic process). The presence of VNAs has been shown to be essential for protection against a productive infection [63,66]. Initial neutralization tests in mice indicated that limited cross-reactivity occurs for LBV and that rabies vaccines might not confer protection [7,8].…”