The long incubation period in rabies: delayed progression of infection in muscle at the site of exposure

Abstract

The striped skunk (Mephitis mephitis) is a host of rabies in large areas of Canada and the United States. In each of two experiments, equal numbers of skunks in two groups were inoculated intramuscularly with low doses of a field strain of rabies virus (street rabies virus). In each experiment, skunks in one group surviving to 2 months were killed at this time and selected tissues were used for examination by the polymerase chain reaction (PCR) method or by immunohistochemistry for rabies antigen. Results of detailed examinations using PCR technology (experiment 1) indicated that muscle at the inoculation site contained viral RNA at 2 months postinoculation, when other relevant tissues on the route of viral migration and early entrance into the central nervous system were negative. The cellular location of virus/antigen, as determined immunohistochemically in experiment 2, was striated muscle fibers and fibrocytes. Our results indicate a major role of muscle (tissue) infection at the inoculation site in the long incubation period of rabies in skunks. These and related findings will be useful in rabies control and, if applicable to other species, will be relevant in postexposure treatment.

Involvement of the Rabies Virus Phosphoprotein Gene in Neuroinvasiveness

“…Previous studies using both street and fixed RABV strains have demonstrated that muscle cells are the infection sites in peripheral tissue (7)(8)(9)(10)45). In this study, we compared in vivo replication efficiencies of the Ni-Luc, Ni-CE-Luc, and CE(NiP)-Luc strains in muscle and obtained data strongly suggesting that the Ni P gene, but not the Ni-CE P gene, mediates stable viral replication in muscle (Fig.…”

“…Previous histopathological studies using animals inoculated with street RABV strains (field isolates) or fixed RABV strains (laboratory and vaccine strains) via the intramuscular (i.m.) route have demonstrated the presence of the viral antigen in muscle cells prior to detection of the antigen in peripheral nerves (7)(8)(9)(10). These observations indicate the possibility that RABV replication in muscle cells contributes to efficient infection of peripheral nerves.…”

Update on rabies

“…[11][12][13][14] A skin biopsy is a useful antemortem diagnostic test in humans because the rabies virus antigen may be detected in nerves adjacent to hair follicles, 15,16 and/or the rabies virus RNA may be detected in the skin biopsy specimen using reverse transcriptionpolymerase chain reaction (RT-PCR) amplification. 17 The most detailed studies of events that take place during the incubation period in a natural model of rabies were performed by Charlton et al 18 in a skunk model. A Canadian isolate of street (wild-type) rabies virus obtained from skunk salivary glands was inoculated into hindlimb abductor digiti quinti muscles of skunks.…”

A Bayesian approach for inferring the dynamics of partially observed endemic infectious diseases from space-time-genetic data

“…However, the epidemiological dynamics of rabies are complicated by two factors. First, rabies has a highly variable incubation period [15,16] and second, rabies has a very large host range that includes all mammals, many of which would play no part in the onward transmission of the virus [14]. In southern Africa, two distinct genetic variants of rabies virus are known to circulate-one among members of the Canidae, including domestic dogs (Canis lupus familiaris), and the other among several members of the Herpestidae [17].…”