A conserved lysine/arginine-rich motif is essential for the autophagic degradation of potyviral 6K1 protein and virus infection

• DOI: 10.1128/jvi.02183-24
• Publication Date: 2025-02-10T14:00:35Z
• Authors: Weiyao Hu; Changhui Deng; Li Qin; Peilan Liu; Linxi Wang; Xaioqing Wang; Wei Shi; Asma Aziz; Fangfang Li; Xiaofei Cheng; Aiming Wang; Zhaoji Dai; Xiaohua Xiang; Hongguang Cui
• Keywords: Tobacco etch virus; Polyproteins; Viral protein

ABSTRACT Potyviruses possess one positive-sense single-stranded RNA genome, mainly dependent on polyprotein processing as the expression strategy. The resulting polyproteins are proteolytically processed by three virus-encoded proteases into 11 or 12 mature proteins. One such factor, 6 kDa peptide 1 (6K1), is an understudied viral factor. Its function in infection remains largely mysterious. This study to reveal part of its roles using pepper veinal mottle virus (PVMV) model. Alanine substitution screening analysis revealed that 15 17 conserved residues across potyviral 6K1 sequences essential for PVMV infection. However, protein less accumulated virus-infected cells, although P3-6K1 and 6K1-CI junctions efficiently NIa-Pro release, indicating undergoes a self-degradation event. Mutating cleavage site prevent abolishes infection, suggesting generation along with degradation might be important multiplication. We corroborated cellular autophagy engaged 6K1’s degradation. Individual engineering variants allows their Five variants, D30A, V32A, K34A, L36A, L39A, significantly interfere five enclosed lysine/arginine-rich motif; four them appear crucial engaging autophagy-mediated self-degradation. Based these data, we envisaged scenario which 6K1s interact unknown anti-viral component co-degraded promote IMPORTANCE Potyvirus largest genus plant-infecting viruses, encompasses socio-economically species, Potato Y , Plum pox Soybean mosaic . Like all picorna-like potyviruses express factors via processing. Theoretically, P3 through CP, including 6K1, should share equivalent number molecules. small size (~6 kDa) but cells. demonstrates In particular, found motif this finding reveals facet helps understand pro-viral role