Rhabdovirus - Replication, Transmission, Pathogenesis, Clinical manifestations

Replication of Rhabdovirus

The replication of the rabies virus occurs/Rhabdovirus in the following steps:

1. Virus adsorption and cell entry

2. Virus penetration and uncoating

3. Transcription

4. Translation

5. Replication, assembly, and budding

The rabies virus replicates in the cytoplasm of the cell. The virus is attached by a glycoprotein spike to the acetylcholine receptor on the cell surface. After receptor binding, the virus enters the cell via the endocytic pathway.

The acidic environment of the endosome induces a change in the conformation of the glycoprotein G that mediated the fusion of the viral envelope with the cellular membrane. The negative sense RNP is then released in the cytoplasm and constitutes the template for viral gene expression and replication by the viral RNA polymerase (the L-P polymerase complex).

During transcription, a positive-stranded leader RNA and five capped and polyadenylated mRNAs are synthesized. The replication process yields nucleocapsids containing full-length positive-sense RNA, which in turn serve as a template for the synthesis of negative-sense RNA.

During their synthesis, the Rhabdovirus genome is encapsidated by the N protein. The neo-synthesized genome RNP either serves as a template for secondary transcription or is transported to the cell membrane and assembled with M and G proteins for the budding of neo-synthesized virions.

Transmission of Rhabdovirus

Rabies is a zoonotic disease and is transmitted by the bite of a rabid dog or infected animals (foxes, wolves, jackals, bats, etc) is the major route of transmission of infection.

Rarely, it is transmitted by contact with saliva with broken skin or with mucus membranes and exposure to aerosolized secretions from an infected animal. Other routes of transmission include corneal transplantation (organ transplant included), and mother-to-child (rare cases).

Pathogenesis of Rhabdovirus

The Rhabdovirus may enter the peripheral nervous system directly at the site of the bite. However, in some cases, it multiplies in muscles and connective tissue at the site of inoculation and then enters the peripheral nerves at the neuromuscular junction.

Then, the virus reaches the CNS and multiplies there causing the death of neural tissue and encephalitis to occur. Later, the virus reaches the salivary glands through the peripheral nervous system. The virus also reaches other organs such as the pancreas, kidney, retina, cornea, etc.

From salivary glands, it is secreted into saliva and transmitted to other hosts during biting.

Steps:

• Virus enters via an animal bite

• Virus replicates in muscle at the site of the bite

• Virus infects a nerve in the peripheral nervous system and moves by retrograde transport

• Virus replicated in dorsal root ganglion and travels up the spinal cord to the brain

• Brain infected

• Virus travels from the brain via nerves to other tissues such as the eye, kidneys, and salivary glands.

Clinical manifestations of Rhabdovirus

The incubation period of the rabies virus is highly variable, ranging from 10 days to more than a year, in most cases 2-10 weeks. The clinical stages can be divided into 3 stages:

• Short prodromal phase

• Acute neurological phase and

• Coma and death

The prodromal phase lasts for 2-10 days after incubation. During this period, non-specific symptoms/clinical syndromes such as headaches. Photophobia, vomiting, sore throat, and fever occur.

The acute neurological phase occurs after the prodromal phase and lasts for 2-7 days. The most common manifestation is so-called “furious” rabies where symptoms of nervous system dysfunction such as biting, hydrophobia, hallucination, increased salivation, etc occur and finally, a coma ensues.

The paralytic (dumb) form of rabies usually starts with prodrome followed by rapidly spreading paralysis. The major cause of death is respiratory paralysis.

Recovery and survival after the appearance of its symptoms are extremely rare.