Global Challenge RNA Viruses

Antibodies against viral proteins

Viral epidemics are one of the greatest challenges of our time. The causative agents of most viral infectious diseases that have occurred in recent decades are RNA viruses. In addition to SARS-CoV-2, these include influenza viruses, Ebola virus, poliovirus, Zika and dengue virus, among others.

RNA viruses hijack the host cell's translational machinery to both optimize viral protein production and subvert RNA surveillance by the host. A thorough understanding of the mechanisms of polysome reconfiguration is the basis for developing vaccines and therapeutics. In a recent study published in Nature, Aviner et al. employed an elegant proteomics strategy combining liquid chromatography-tandem mass spectrometry (LC-MS/MS) with functional genomics and pharmacological manipulation to study how poliovirus (PV), Zika virus (ZIKV), and dengue virus (DENV) remodel polysomes after infection. The results reveal both common and distinct mechanisms of polysome reconfiguration in RNA viruses that do not involve changes in ribosomal core composition, but rather involve virus-dependent association of hundreds of host cell factors with the translational machinery. These include viral surveillance factors, translation initiation proteins, helicases, and proteostasis components. Of particular intrigue is the involvement of ER collagen prolyl hydroxylases in the cotranslational modification of nascent ZIKV and DENV polyproteins, inhibition of which leads to a reduction in viral titer.

Four viral protein antibodies from our partner company GeneTex were used in this work:

GTX133309	Zika virus NS3 protein antibody
GTX133312	Zika virus NS5 protein antibody
GTX127277	Dengue virus Envelope protein antibody
GTX124252	Dengue virus NS3 protein antibody