Protein Interactions during the Flavivirus and Hepacivirus Life Cycle

Abstract

Protein-protein interactions govern biological functions in cells, in the extracellular milieu, and at the border between cells and extracellular space. Viruses are small intracellular parasites and thus rely on protein interactions to produce progeny inside host cells and to spread from cell to cell. Usage of host proteins by viruses can have severe consequences apoptosis, metabolic disequilibria, or altered cell proliferation and mobility. Understanding protein interactions during virus infection can thus educate us on viral infection and pathogenesis mechanisms. Moreover, it has led to important clinical translations, including the development of new therapeutic and vaccination strategies. Here, we will discuss protein interactions of members of the family, which are small enveloped RNA viruses. Dengue virus, Zika virus and hepatitis C virus belong to the most prominent human pathogenic With a genome of roughly ten kilobases encoding only ten viral proteins, display intricate mechanisms to engage the host cell machinery for their purpose. In this review, we will highlight how dengue virus, hepatitis C virus, Japanese encephalitis virus, tick-borne encephalitis virus, West Nile virus, yellow fever virus, and Zika virus proteins engage host proteins and how this knowledge helps elucidate infection. We will specifically address the protein composition of the virus particle as well as the protein interactions during virus entry, replication, particle assembly, and release from the host cell. Finally, we will give a perspective on future challenges in interaction proteomics and why we believe these challenges should be met.

Tick-Pathogen Interactions and Vector Competence: Identification of Molecular Drivers for Tick-Borne Diseases

“…The IMD pathway is involved in protection against infection in arthropods, but recent results support the existence of two functionally distinct IMD circuits in insects and ticks (Shaw et al, 2017). Future comparative analyses between different vector species will provide additional information on the functional implication of the different biological processes in vector-pathogen interactions and vector competence (Gerold et al, 2017). …”

Glycomics and Proteomics Approaches to Investigate Early Adenovirus–Host Cell Interactions

“…Previously, AE-MS has successfully identified host factor interactions with viral non-structural proteins of virus families ranging from flaviviruses to herpesviruses (reviewed in Refs. [133,[147][148][149]). The application to virus receptor discovery is now in reach (Fig.…”

Real Time Analysis of Bovine Viral Diarrhea Virus (BVDV) Infection and Its Dependence on Bovine CD46

“…This might suggest that another interaction partner on the cellular surface-for example heparan sulphate or an as of yet unidentified attachment factor-might be responsible for coupling to the underlying actin network and that CD46 is rather involved in deceleration of particle transport on the cell surface or the anchoring of particles at potential sites of endocytosis. The importance of attachment factors such as heparan sulphate has also been demonstrated for other members of the Flaviviridae (reviewed in [29]). Also, CD46 is not sufficient to render cell lines derived from non-cloven-hoofed animals or humans susceptible to infection with BVDV.…”