International Centre for Genetic Engineering & Biotechnology, New Delhi-110067, India.
The avian influenza virus H5N1 is a “moving target” which shows a wide variety of variation from extent of pathogenesis to variation of isolates from different parts of the world. Further there are isolates from infected humans to domestic animals to wild birds. With all these variants of avian influenza virus, it is important to identify specific sequence changes associated with their variations. However, besides identification of sequence changes alone, it is of great importance to identify host protein interaction profiles. With minute changes that take place in the sequences as the virus evolves, it is important to understand how the corresponding host protein interaction profile has changed over the years. This data when co-related with the extent of pathogenicity and evolved capabilities of the virus to jump species, gives us a great deal of information on the strategic evolutionary course the virus. In order to map changes in host-virus interaction profiles from the continuously evolving H5N1 virus, we intend to focus on individually cloned genes of the Indian isolate and identify their host interaction partners. To begin with, we have focused on the 498 amino acid nucleocapsid (NP) protein, which shows single-stranded RNA binding activity responsible for viral encapsidation. NP has also been postulated to be involved in nuclear import and export of the genome, interaction with viral polymerase, interaction with matrix protein and interaction with the CRM-1 protein. These previous reports hint clearly that NP possibly has many interactions with its host proteins. In order to investigate the role of NP in various host-viral interactions, we conducted a yeast two-hybrid screen using a human cDNA lung library and have identified many new interaction partners. Through this investigation, we have uncovered an important virus-host interaction which may hold the potential for being a target for anti-viral approaches.
