Replication Of Rabies Viruses

The virus is typically present in the nerves and saliva of a symptomatic rabid animal (Turton and Jenny, 2000). The route of infection is usually, but not always, by a bite. In many cases the infected animal is remarkably aggressive, may attack without provocation, and exhibits otherwise uncharacteristic behavior. Transmission between humans is extremely rare. A few cases have been recorded through transplant surgery ( Srinivasan et al., 2009). After a typical human infection by bite, the virus enters the peripheral nervous system. It then travels along the nerves towards the central nervous system (Jackson and Wunner, 2002). During this phase, the virus cannot be easily detected within the host, and vaccination may still confer cell-mediated immunity to prevent symptomatic rabies. When the virus reaches the brain, it rapidly causes encephalitis. This is called the prodromal phase, and is the beginning of the symptoms. Once the patient becomes symptomatic, treatment is almost never effective and mortality is over 99%. Rabies may also inflame the spinal cord producing transverse myelitis

The steps in the lytic replication cycle of an enveloped virus are illustrated for rabies virus, which has a single-stranded RNA genome.

step 1

The structural components of this virus are depicted at the top. The nucleocapsid of this virus is helical rather than icosahedral.

step 2

After a virion adsorbs to a specific host membrane protein the cell engulfs it in an endosome

steps 3

A protein in the endosome membrane pumps protons from the cytosol into the endosome interior.

Step 4

The resulting decrease in endosomal pH induces a conformational change in the viral glycoprotein, leading to fusion of the viral envelope with the endosomal lipid bilayer membrane and release of the nucleocapsid into the cytosol

step 5

Viral RNA polymerase uses ribonucleoside triphosphates in the cytosol to replicate the viral RNA genome

step 6

synthesize viral mRNAs One of the viral mRNAs encodes the viral transmembrane glycoprotein (blue), which is inserted into the lumen of the endoplasmic reticulum (ER)

step 7

it is synthesized on ER-bound ribosomes

step 8

Carbohydrate is added to the large folded domain inside the ER lumen and is modified as the membrane and the associated glycoprotein pass through the Golgi apparatus.

step 9

Vesicles with mature glycoprotein fuse with the plasma membrane, depositing viral glycoprotein on the cell surface with the large folded domain outside the cell, the transmembrane α helix spanning the plasma membrane, and the small cytoplasmic domain within the cell

step 10

Meanwhile, other viral mRNAs are translated on host-cell ribosomes into nucleocapsid protein, matrix protein, and viral RNA polymerase

step 11

These proteins are assembled with replicated viral genomic RNA (dark red) into progeny nucleocapsids

step 12

then associate with the viral transmembrane glycoprotein in the plasma membrane

step 13

As additional copies of the matrix protein on a single nucleocapsid associate with the cytoplasmic domain of additional copies of the viral transmembrane glycoprotein, the plasma membrane is folded around the nucleocapsid, forming a “bud” that eventually is released