Host–pathogen interactome analysis of Chikungunya virus envelope proteins E1 and E2

Abstract

The envelope proteins of Chikungunya virus (CHIKV) are known to play crucial roles in viral infection and spread. Although the role of envelope proteins in viral infection has been studied, the cellular interactors of these proteins are still elusive. In the present study, the ectodomains of CHIKV envelope proteins (E1 and E2) have been used for a high throughput yeast two-hybrid (Y2H) screening to identify the interacting host protein partners. Following a comparative analysis between the viral-host protein interaction data generated from Y2H and computational approach, five host proteins interacting with E1 and three host proteins interacting with E2 common to both datasets were identified. These associations were further verified independently by pull down and protein interaction ELISA. The identified interactions shed light on the possible cellular machinery that CHIKV might be employing during viral entry, trafficking, and evasion of immune system.

The Interplay of Viral and Host Factors in Chikungunya Virus Infection: Targets for Antiviral Strategies

“…In addition, ATP synthase β subunit was found to be involved in the entry of CHIKV into Aedes aegypti mosquito cell lines [127]. Additional host factors like protein tyrosine phosphatase non-receptor type 2 (PTPN2), fibril-forming collagen (COL1A2), and actin gamma 1 (ACTG1) were also shown to interact with the E2 proteins in immunoprecipitation experiments [128]. However, further mechanistic studies are required to understand the role of these proteins during CHIKV infection.…”

“…In an attempt to uncover host proteins that interact with E1, Dudha and colleagues performed a yeast two-hybrid (Y2H) screening on a human brain cDNA library [128]. The screen was able to identify 5 interacting host proteins (copper metabolism (Murr1) domain containing 1 (COMMD1), thrombospondin 1 (THBS1), dynein, cytoplasmic 1, heavy chain 1 (DYNC1H1), ATPase Na1/K1 transporting beta 3 polypeptide (ATP1B3), and microtubule-associated protein 1B (MAP1B)).…”

“…Of these, four hits (COMMD1, THBS1, DYNC1H1, and ATP1B3) passed and were validated via immunoprecipitation and ELISA [128]. However, the biological significance and exact mechanisms of the interactions have yet to be explored.…”

“…Hepatitis C virus nonstructural 3/4A protease cleaves PTPN2 that induces a shift from host Th1 to Th2 immune response. [128,218] COL1A2…”

“…Shown to increase infectious viral titer of Sindbis virus (SINV) and also proposed to aid in its transmission. [128,219] ACTG1 ACTG1: Part of cellular trafficking machinery.…”