The study findings are the role of estrogen receptors in regulating Zika virus infection; and how human papillomavirus (HPV) causes cancer. At the molecular level, viruses invade cells and manipulate them to replicate, survive, and cause disease. Since they depend on human cells for their life cycle, one way viruses co-opt cellular machinery is through protein-protein interactions within their cell host.
Similarly, cells respond to infection by initiating immune responses that control and limit viral replication these too, depend on protein-protein interactions. To date, considerable effort has been invested in identifying these key interactions and many of these efforts have resulted in many fundamental discoveries, some with therapeutic implications.
Using a novel algorithm, P-HIPSTer exploits protein structural information to systematically interrogate virus human protein-protein interactions with remarkable accuracy. By applying P-HIPSTer to all 1,001 human-infecting viruses; and the approximately 13,000 proteins they encode. The algorithm predicted roughly 280,000 likely pairs of interacting proteins; that represent a comprehensive catalogue of human virus protein, protein interactions with an accuracy rate of almost 80%.
Viruses invade cells
The researchers finding that Zika virus interacting with estrogen receptor; the protein that allowing cells to effectively respond to the estrogen hormone. Importantly, they found estrogen receptor has potential to inhibit Zika virus replication. As estrogen receptor inhibits viral replication even more than interferon, a protein that is the body’s first line of defense to viral infection and our gold standard for anti-viral defense.
The finding is particularly relevant to clinical disease as pregnant women are most susceptible to Zika during their first trimester, which is when estrogen levels are at their lowest. This period also is when the fetus is most susceptible to Zika, a virus for which there is no vaccine or specific treatment and that can cause sever birth defects.
Interactions mediated by viruses
The researchers also examined whether the interactions mediated by viruses have impacted human genetics. The researchers finding evidence of strong selection pressure for several dozen cellular proteins have been shaping by viral infection; unlocking new insights into how our genome has been impacting by viruses. In the future, the algorithm could also be using to explore viruses or pathogens; that effect agricultural plants or livestock.
However, the genetic and molecular circuitry at the interface of host-pathogen interactions. But a deeper understanding of these relationships; provides important insights into cellular machinery that control basic cell biology and has broad implications in human translational immunology; and infectious disease research.