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Unveiling the interactome of African swine fever virus Entry–Fusion complex proteins and infection mechanisms
1 , 2 , 1 , 3 , * 1
1  Biotechnology, INIA-CSIC, Madrid, España
2  Centro Nacional de Microbiología (CNM) Instituto de Salud Carlos III (ISCIII), Madrid, España
3  Institute of Infection, Veterinary & Ecological Sciences Faculty of Health and Life Sciences
Academic Editor: Eric Freed

Published: 09 March 2026 by MDPI in Viruses 2026 – New Horizons in Virology session Virus-Host Interactions
Abstract:

African swine fever (ASF) is a highly contagious and lethal hemorrhagic disease caused by the African swine fever virus (ASFV), a complex nucleocytoplasmic large DNA virus (NCLDV) characterized by its multilayered envelope and linear double-stranded DNA genome (1). This devastating virus infects both wild and domestic suids, posing a significant threat to global swine industries and agricultural stability. Despite its profound socio-economic impact, effective vaccines or antiviral treatments for ASFV are currently lacking, highlighting an urgent need for innovative strategies to combat this disease. Central to this objective is comprehensive understanding of the molecular mechanisms underlying ASFV infection.

While the intricacies of ASFV entry into host cells remain incompletely understood, emerging evidence suggests a complex interplay involving endocytosis and endosomal trafficking preceding viral fusion events and replication. Recent investigations have suggested the existence of an entry–fusion complex (EFC) within ASFV, sharing structural similarities with analogous complexes identified in related viruses such as the vaccinia virus. However, the composition of this complex, particularly the larger components such as viral topoisomerase II P1192R and G1340L, remains poorly characterized.

The study aims to elucidate the functional roles of these viral EFC proteins using mass spectrometry (MS) analysis and the data obtained, which was processed and analyzed using the Perseus software. Other techniques such as Western blot and immunoprecipitation assay were performed to validate the results; we also performed a functional assay using inhibitors. Our preliminary findings implicated G1340L in nucleic acid metabolism and in the HSP90 cycle for steroid hormone receptor (SHR), whereas P1192R appears to be involved in mRNA processing and ribosome biogenesis. Unraveling the intricacies of these proteins promises to provide crucial insights into the ASFV infection process, offering invaluable targets for the development of antiviral therapeutics.

Keywords: ASFV interactome G1340L P1192 MAT2A
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