Transmission of rabies virus usually begins when the infected saliva of a host is passed to an uninfected animal.

Various routes of transmission have been documented and include contamination of mucous membranes (i.e., eyes, nose, mouth), aerosol transmission, and corneal transplantations. The most common mode of rabies viral transmission is through the bite and virus-containing saliva of an infected host.

Following primary infection, the virus undergoes an eclipse phase in which it cannot be easily detected within the host. This phase may last for several days or months. Investigations have shown evidence for direct entry of virus into peripheral nerves at the site of infection, as well as evidence for indirect entry after viral replication in nonnervous tissue (i.e., muscle cells). It is during this time that host immune defenses may play a role in the outcome of viral infection because rabies viral antigens are good simulators of cell-mediated immunity. The uptake of virus into peripheral nerves is important for a progressive infection to occur.

Following uptake into peripheral nerves, rabies virus is transported to the central nervous system (CNS) via retrograde axoplasmic flow. Typically this occurs via sensory and motor nerves involved at the initial site of infection. The incubation period (number 4 in figure) is the time of exposure to onset of clinical signs of disease. The incubation period may vary from a few days to several years, but typically lasts 1 to 3 months. Dissemination of virus within the CNS is rapid, with early involvement of limbic system neurons. Active cerebral infection is followed by the passive centrifugal spread of virus to peripheral nerves. The amplification of infection within the CNS occurs through cycles of viral replication and cell-to-cell transfer of progeny virion. Centrifugal spread of virus may lead to the invasion of highly innervated nerve sites of various tissues, including the salivary glands. It is during this period of cerebral infection that classic behavioral changes develop.

Information courtesy of the Centers for Disease Control.