Pathogenesis of bat rabies in a natural reservoir: Comparative susceptibility of the straw-colored fruit bat (Eidolon helvum) to three strains of Lagos bat virus.

Rabies is a fatal neurologic disease caused by lyssavirus infection. People are infected through contact with infected animals. The relative increase of human rabies acquired from bats calls for a better understanding of lyssavirus infections in their natural hosts. So far, there is no experimental model that mimics natural lyssavirus infection in the reservoir bat species. Lagos bat virus is a lyssavirus that is endemic in straw-colored fruit bats (Eidolon helvum) in Africa. Here we compared the susceptibility of these bats to three strains of Lagos bat virus (from Senegal, Nigeria, and Ghana) by intracranial inoculation. To allow comparison between strains, we ensured the same titer of virus was inoculated in the same location of the brain of each bat. All bats (n = 3 per strain) were infected, and developed neurological signs, and fatal meningoencephalitis with lyssavirus antigen expression in neurons. There were three main differences among the groups. First, time to death was substantially shorter in the Senegal and Ghana groups (4 to 6 days) than in the Nigeria group (8 days). Second, each virus strain produced a distinct clinical syndrome. Third, the spread of virus to peripheral tissues, tested by hemi-nested reverse transcriptase PCR, was frequent (3 of 3 bats) and widespread (8 to 10 tissues positive of 11 tissues examined) in the Ghana group, was frequent and less widespread in the Senegal group (3/3 bats, 3 to 6 tissues positive), and was rare and restricted in the Nigeria group (1/3 bats, 2 tissues positive). Centrifugal spread of virus from brain to tissue of excretion in the oral cavity is required to enable lyssavirus transmission. Therefore, the Senegal and Ghana strains seem most suitable for further pathogenesis, and for transmission, studies in the straw-colored fruit bat

Distribution of Lagos bat virus antigen in the brains of experimentally infected bats.

<p>Distribution of Lagos bat virus antigen in the brains of experimentally infected bats.</p

Lyssavirus antigen expression in neurons infected with different strains of Lagos bat virus.

<p>All sections immunostained for lyssavirus antigen. Original magnification: x100 (<b>A</b>, <b>B</b> and <b>C</b>). <b>A</b>: Senegal strain, relatively large number of neurons are infected, small cytoplasmic antigen (red) granules, infected neurons have variable numbers of granules (Bat 6). <b>B</b>: Nigeria strain, relatively large number of neurons are infected, large cytoplasmic antigen (red) granules, infected neurons have similar numbers of granules (Bat 9). <b>C</b>: Ghana strain, relatively few neurons infected, small cytoplasmic antigen (red) granules (Bat 12).</p

Lyssavirus antigen expression in neurons infected with different strains of Lagos bat virus.

<p>All sections immunostained for lyssavirus antigen. Original magnification: x 100 (<b>A</b>, <b>B</b> and <b>C</b>); x40 (<b>D</b>); x100 (inset of <b>D</b>) <b>A</b>: Taste bud (between short arrows) bordering the lumen of the oral cavity (indicated with asterisk) in cross section of tongue. Several neuroepithelial cells within the taste bud have small cytoplasmic antigen (red) granules. Epithelial cells directly adjacent to taste buds also occasionally have antigen granules (indicated with long arrow) (Bat 6). <b>B</b>: Three neurons in a ganglion within the connective tissue of a salivary gland. One neuron has small cytoplasmic antigen (red) granules (Bat 12). <b>C</b>: Neurons in a ganglion within the connective tissue of the epicardium (heart). One neuron has abundant small cytoplasmic antigen (red) granules. Directly adjacent one neuron with less antigen granules (Bat 6). <b>D</b>: Neurons within the myenteric plexus (intestine) have abundant small cytoplasmic antigen (red) granules. Asterisk indicates the serosa side of the intestinal wall (bat 11). Inset contains a higher magnification of the image in the square of <b>D</b>.</p

Distribution of Lagos bat viral RNA and antigen in tissues of experimentally infected bats.

<p>Distribution of Lagos bat viral RNA and antigen in tissues of experimentally infected bats.</p

Neuronal routes different Lagos bat viruses travelled from the intracranial inoculation site to the periphery.

<p>Neuronal routes different Lagos bat viruses travelled from the intracranial inoculation site to the periphery.</p

Presence (+) or absence (-) of clinical signs in bats inoculated with Lagos bat virus.

<p>Presence (+) or absence (-) of clinical signs in bats inoculated with Lagos bat virus.</p