Journal of Tropical Diseases & Public Health

Transmission, Proliferation and Viral Entry of Lyssavirus

Ivan Vega^* Department of Pathology, University Hospital of Araba, Vitoria-Gasteiz, Spain
^*Correspondence: Ivan Vega, Department of Pathology, University Hospital of Araba, Vitoria-Gasteiz, Spain, Email:

Received: 02-Sep-2022, Manuscript No. JTD-22-18356; Editor assigned: 06-Sep-2022, Pre QC No. JTD-22-18356 (PQ); Reviewed: 23-Sep-2022, QC No. JTD-22-18356; Revised: 30-Sep-2022, Manuscript No. JTD-22-18356 (R); Published: 07-Oct-2022, DOI: 10.35248/2329-891X.22.10.349

Description

The lyssaviruses that cause rabies, possibly the deadliest encephalitic disease ever recorded, are known. All terrestrial mammals are expected to be susceptible to infection by the rabies lyssavirus prototype (RABV). The most common method of transmission is through the bite of an infected animal, although it can also happen through other means such scratches, in rare cases, organ transplants, and other means. Presently, there are 17 recognised viral species in the genus Lyssavirus (family Rhabdoviridae) and one potential species. The negative sense RNA genomes of all lyssaviruses are around 11 000 nucleotide long bullet-shaped particles. The nucleoprotein, phosphoprotein, matrix protein, glycoprotein, and polymerase (5'-N-P-M-G-L-3') with a 5'-3' transcriptional bias are the five structural proteins that are encoded by the genome. Together with the P and L proteins, the N protein encapsidates the viral RNA to create the Ribonucleoprotein (RNP) complex, which can start viral transcription and replication. During replication, the M protein attracts the RNP to the cellular membrane and compresses it into the distinctive bullet form. The G protein, also known as the transmembrane spike protein, which is the main antigenic determinant, particularly interacts with the M protein to facilitate the budding of the enveloped virus from the cell.

Not only is RABV the type species for the genus, but it also poses the biggest risk to public health of any lyssavirus. However, a number of other terrestrial mammalian species, particularly carnivores such raccoons, skunks, foxes, and jackals, can continue transmission. Domestic dogs are the principal reservoir for RABV in dog-rabies endemic countries.

Viral infection is most frequently transmitted through the bite of an infected animal, which injects saliva containing the virus into the muscle or other peripheral tissue. Following inoculation, RABV normally infects muscle cells, where it replicates slowly. This is likely to be assisted by the nicotinic acetylcholine receptor. It's possible that the virus's varied localization at the injection site is a factor in the varying incubation period that characterises rabies. In contrast, RABV can infect motor endplates without the first replication in the muscle in cases where the inoculum concentration is higher. Through motor endplates at the neuromuscular junction, RABV enters the Peripheral Nervous System (PNS), although the precise mechanism by which the virus internalises is still unknown.

Through the PNS and into the CNS, RABV is transported through microtubule-dependent retrograde rapid axonal transport. The virus moves across neurons, reproduces, and keeps moving toward the central nervous system and the brain. The p75NTR receptor, which is not necessary for infection but promotes targeted and quicker transport of RABV to the CNS, aids in this neuronal dissemination. The M protein makes it easier for microtubules to depolymerize, which increases the effectiveness of viral transcription and replication. The L protein manipulates microtubules to boost transport efficiency. While evidence suggests that RABV undergoes active, G protein- dependent anterograde transport in peripheral neurons, such as Dorsal Route Ganglion (DRG) neurons, at a rate three times faster than that of retrograde transport, retrograde transport is thought to occur at an approximate rate of 50 to 100 mm per day in humans with species-dependent variation.

Although the significance of this anterograde transport mechanism is unclear, recent evidence indicates that it is crucial for the spread of RABV through the PNS (including to non- neuronal organs) following centrifugal spread from the CNS. This is in contrast to earlier data that suggested that RABV spreads exclusively by axonal and trans-synaptic transport in the retrograde direction. Once in the CNS, RABV continues to spread via retrograde axonal transport thought to be facilitated by metabotropic glutamate receptor subtype 2, which is a cellular entry receptor that is abundant throughout the Central Nervous System (CNS). The virus reaches the brainstem and subsequently the brain, where it proliferates and clinical symptoms manifest. It spreads to the salivary glands along terminal axons via anterograde transport where it continues to proliferate and is subsequently shed in the saliva for transmission to another host. RABV can spread to peripheral, non-neuronal organs anterograde transport, and can be detected in these sites after the onset of clinical symptoms.