Structural and Molecular Virology Group

Host-cell interactions by Hepatitis A virus

Hepatitis A virus (HAV) is a non-enveloped, single-stranded RNA virus belonging to the family picornaviridae, that causes acute viral hepatitis. The virus is extremely slow growing in culture, and this has hampered studies on understanding virus-host interactions. To circumvent this problem, we are using individual viral proteins and peptides to elucidate some of the unknown aspects regarding HAV biology. Chief amongst them is the manner of host cell interaction and host membrane breaching by the virus, which is the first step in any virus infection cycle (Shukla et al, 2014). We are also studying the roles of HAV non-structural proteins in establishment of infection and immune system evasion (Shukla et al, 2015).

 

Mechanism of viral entry and genome release in Flock House Virus and development of virus-based nanoparticles

Flock House Virus derives its peculiar name from a former agriculture research station in New Zealand, called Flock House, in whose environs it was originally isolated from dead insects. What drew us to this virus, besides its wacky name, was that it is an excellent model system to study the basic and applied aspects of non-enveloped virus biology. It is a simple virus – it lacks a lipid envelope, is made up of multiple copies of a single capsid protein, contains a bipartite, single-stranded RNA genome, and is non-infectious to humans.

We have utilized the host cell-membrane penetration by the FHV gamma peptide as a model system to provide a structural basis to the molecular mechanisms of host cell membrane interaction by non-enveloped viruses (Bajaj et al, 2016). We are also engineering FHV into a nano-vehicle for biomedical purposes such as drug delivery and antigen display (Bajaj and Banerjee, 2016).

 

Host cell interaction by Chikungunya virus

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that is responsible for causing widespread outbreaks of incapacitating viral disease almost every year in India. While the disease is prevalent in Africa and Asia, cases have also been reported in Europe and America. A thorough understanding of the viral life cycle is essential for the development of therapeutics.

We are investigating the disassembly pathway of CHIKV using a combination of cryoelectron microscopy, biophysical techniques and Molecular Dynamics simulation. We are also characterizing CHIKV components known to interact with host factors. The overall intent is to use these studies in designing effective anti-virals against Chikungunya fever.