Reviewing Chandipura: a vesiculovirus in human epidemics

Abstract

Chandipura virus, a member of the rhabdoviridae family and vesiculovirus genera, has recently emerged as human pathogen that is associated with a number of outbreaks in different parts of India. Although, the virus closely resembles with the prototype vesiculovirus, Vesicular Stomatitis Virus, it could be readily distinguished by its ability to infect humans. Studies on Chandipura virus while shed light into distinct stages of viral infection; it may also allow us to identify potential drug targets for antiviral therapy. In this review, we have summarized our current understanding of Chandipura virus life cycle at the molecular detail with particular interest in viral RNA metabolisms, namely transcription, replication and packaging of viral RNA into nucleocapsid structure. Contemporary research on otherwise extensively studied family member Vesicular Stomatitis Virus has also been addressed to present a more comprehensive picture of vesiculovirus life cycle. Finally, we reveal examples of protein economy in Chandipura virus life-cycle whereby each viral protein has evolved complexity to perform multiple tasks.

Fig. 1

(a) A schematic presentation of bullet shaped Chandipura virus with glycoprotein G protruding out of the viral envelope. (b) A proposed view of Chandipura virus genome RNA encapsidated with Nucleocapsid protein. Nucleocapsid protein binds to viral RNA to enclose it in a disc like structure. This disc like structures stacks on each other to generate a helical assembly, as depicted, to form core nucleocapsid. Phosphoprotein P and Large Protein L remain associated with N-RNA

Fig. 2

A Schematic depiction of specific yet processive encapsidation of Chandipura virus genome RNA by Nucleocapsid protein N. The picture describes self-assembly of N protein monomer into oligomer that binds to leader RNA or unrelated RNA. Dissociating detergents such as deoxycholate disrupts those oligomer into monomer units and also prevents further oligomerisation. Phosphoprotein P associates with N to keep N protein in a monomer form. This monomer N is able to recognize specific sequence present on leader chain in the nucleation step (I) and is recruited to the viral RNA with concomitant release of P. Subsequently, additional N molecules associates with RNA bound N monomers in the elongation phase (II). N polymerization mediates a conformational change, thus, generates broad specificity within RNA binding interface of N protein and allows for progressive encapsidation to enclose RNA into a helical conformation. This model posit important role of N polymerization on its RNA binding specificity and encapsidation. A proposed stem-loop structural element within leader sequence has also been depicted

Fig. 3

RNA synthesis events of Chandipura Virus. Viral polymerase composed of L and phosphorylated form of P protein transcribes the genome RNA with progressive attenuation at each intergenic region (Int Region) to synthesize leader RNA and five capped and poly adenylated mRNA. RdRp was proposed to remain associated with N-RNA while transcribing the genomic template and reinitiate synthesis of downstream genes after termination. However, during replication mode, the same polymerase read-through the termination signals present at the intergenic region to eventually copy the entire genome. N protein is recruited on nascent genome RNA to protect it form cellular RNase action as it is synthesized. Unphosphorylated form of Phosphoprotein recruited to leader RNA has been proposed to modulate polymerase activity during replication to bring about anti-termination