The following is a summary of “Interactome profiling of Crimean-Congo hemorrhagic fever virus glycoproteins,” published in the November 2023 issue of Infectious Disease by Dai et al.

The urgency surrounding research and development efforts for the Crimean-Congo hemorrhagic fever virus (CCHFV), classified as a biosafety level-4 pathogen, underscores the significance of understanding its molecular interactions. The viral glycoproteins Gn and Gc are pivotal in the CCHFV life cycle through interactions with host cells, yet the precise nature of these interactions has remained largely elusive. In this study, researchers analyzed the cellular interactomes of CCHFV glycoproteins, identifying 45 host proteins as high-confidence interactors with Gn/Gc.

These host proteins participate in various cellular biological processes that link to the physiological functions of the viral glycoproteins. Notably, the study group delved into the role of a specific cellular protein, HAX1. HAX1’s interaction with Gn occurs via its C-terminal region, while its N-terminal section directs Gn to localize within mitochondria. This robust interaction leads to the sequestration of Gn within mitochondria, disrupting its normal Golgi localization critical for functional glycoprotein-mediated progeny virion packaging.

This disruption caused by HAX1 significantly inhibits viral packaging and subsequent propagation, as evidenced in both pseudotyped and authentic CCHFV infections within cellular and animal models. Collectively, their findings offer a comprehensive map of CCHFV Gn/Gc-cell protein-protein interactions and unveil a HAX1/mitochondrion-associated antiviral mechanism employed by the host. These discoveries hold the potential to advance further investigations into CCHFV biology and may inform the development of therapeutic approaches targeting this deadly pathogen.

Source: nature.com/articles/s41467-023-43206-1