TRIM26-mediated degradation of nucleocapsid protein limits porcine reproductive and respiratory syndrome virus-2 infection

• DOI: 10.1016/j.virusres.2022.198690
• Publication Date: 2022-01-22T07:42:43Z
• Authors: Pandeng Zhao; Huiyuan Jing; Wang Dong; Erzhen Duan; Wenting Ke; Ran Tao; Yang Li; Sufang Cao; Haihua Wang; Yan Zhang; Yanting Sun; Jinhe Wang
• Keywords: 0303 health sciences; Swine; Porcine reproductive and respiratory syndrome virus (PRRSV); Porcine Reproductive and Respiratory Syndrome; Replication; Infectious and parasitic diseases; RC109-216; Nucleocapsid Proteins; Virus-host interactions; Virus Replication; Microbiology; Antiviral Agents; QR1-502; 3. Good health; 03 medical and health sciences; Macrophages, Alveolar; Nucleocapsid (N) protein; Animals; Porcine respiratory and reproductive syndrome virus; Tripartite motif 26 (TRIM26)

Porcine reproductive and respiratory syndrome (PRRS), caused by PRRSV, has ranked among the most economically important veterinary infectious diseases globally. Recently, tripartite motif (TRIMs) family members have arisen as novel restriction factors in antiviral immunity. Noteworthy, TRIM26 was reported as a binding partner of IRF3, TBK1, TAB1, and NEMO, yet its role in virus infection remains controversial. Herein, we showed that TRIM26 bound N protein by the C-terminal PRY/SPRY domain. Moreover, ectopic expression of TRIM26 impaired PRRSV replication and induced degradation of N protein. The anti-PRRSV activity was independent of the nuclear localization signal (NLS). Instead, deletion of the RING domain, or the PRY/SPRY portion, abrogated the antiviral function. Finally, siRNA depletion of TRIM26 resulted in enhanced production of viral RNA and virus yield in porcine alveolar macrophages (PAMs) after PRRSV infection. Overexpression of an RNAi-resistant TRIM26 rescue-plasmid led to the acquisition of PRRSV restriction in TRIM26-knockdown cells. Together, these data add TRIM26 as a potential target for drug design against PRRSV.