PhyloProteomic Analysis of Functional Domain Evolution in H7N9 Influenza
Mentor 1
Dr. Robert Kuzoff
Location
Union Wisconsin Room
Start Date
24-4-2015 2:30 PM
End Date
24-4-2015 3:45 PM
Description
Influenza is a swiftly evolving viral pathogen that is capable of infecting a broad range of hosts. Influenza is notorious as being one of the deadliest viruses afflicting humans annually. In recent years, H7N9, a subtype of class A influenza that is normally found only in birds, has acquired the ability to infect humans and has emerged as a source of severe respiratory illness in widespread provinces of eastern China. We employed a battery of bioinformatic methods to examine the complete proteomes of H7N9 isolates recovered from NCBI and IDB databases. Orthologous proteins were aligned and analyzed to assess phylogenetic relationships among them. Resolved clades sorted primarily by host species, but some noteworthy interspecific transmissions were detected. A survey of randomly selected avian and human isolates indicated a suite of sites in the aligned protein sequences that showed consistent differences between sampled species. A detailed review of available literature and selected databases (e.g., PDB, Pfam, and SMART) revealed that several of the variable sites coincided with functional domains or positions known to impact virulence. The locations of the variable sites in resolved structures of influenza proteins were assessed using PyMol 1.7.4. Variable sites that mapped to surface regions of surface glycoproteins, hemagglutinin and neuraminidase, or to the outer envelope’s ion channel, M2, may be immunogenic. If so, variation at these sites could enable sampled H7N9 strains to evade host defenses and propagate more efficiently in human hosts. In summary, we detected a set of positions in proteins sequences that are evolving rapidly and have either known or probable consequences for the virulence and transmissibility of H7N9 in humans.
PhyloProteomic Analysis of Functional Domain Evolution in H7N9 Influenza
Union Wisconsin Room
Influenza is a swiftly evolving viral pathogen that is capable of infecting a broad range of hosts. Influenza is notorious as being one of the deadliest viruses afflicting humans annually. In recent years, H7N9, a subtype of class A influenza that is normally found only in birds, has acquired the ability to infect humans and has emerged as a source of severe respiratory illness in widespread provinces of eastern China. We employed a battery of bioinformatic methods to examine the complete proteomes of H7N9 isolates recovered from NCBI and IDB databases. Orthologous proteins were aligned and analyzed to assess phylogenetic relationships among them. Resolved clades sorted primarily by host species, but some noteworthy interspecific transmissions were detected. A survey of randomly selected avian and human isolates indicated a suite of sites in the aligned protein sequences that showed consistent differences between sampled species. A detailed review of available literature and selected databases (e.g., PDB, Pfam, and SMART) revealed that several of the variable sites coincided with functional domains or positions known to impact virulence. The locations of the variable sites in resolved structures of influenza proteins were assessed using PyMol 1.7.4. Variable sites that mapped to surface regions of surface glycoproteins, hemagglutinin and neuraminidase, or to the outer envelope’s ion channel, M2, may be immunogenic. If so, variation at these sites could enable sampled H7N9 strains to evade host defenses and propagate more efficiently in human hosts. In summary, we detected a set of positions in proteins sequences that are evolving rapidly and have either known or probable consequences for the virulence and transmissibility of H7N9 in humans.
