2. Academic Validation
  3. Palmitoylation of KSHV pORF55 is required for Golgi localization and efficient progeny virion production

Palmitoylation of KSHV pORF55 is required for Golgi localization and efficient progeny virion production

  • PLoS Pathog. 2024 Apr 16;20(4):e1012141. doi: 10.1371/journal.ppat.1012141.
Yaru Zhou 1 2 3,  Xuezhang Tian 1 2,  Shaowei Wang 1 2,  Ming Gao 1 2,  Chuchu Zhang 1 2,  Jiali Ma 1 2,  Xi Cheng 1 2,  Lei Bai 4,  Hai-Bin Qin 5 6,  Min-Hua Luo 5 6,  Qingsong Qin 7,  Baishan Jiang 2,  Ke Lan 2 4,  Junjie Zhang 1 2 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, State Key Laboratory of Virology, Medical Research Institute, Wuhan University, Wuhan, China.
  • 2 Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Wuhan University, Wuhan, China.
  • 3 Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Province Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, China.
  • 4 State Key Laboratory of Virology, School of Life Sciences, Wuhan University, Wuhan, China.
  • 5 State Key Laboratory of Virology, CAS Center for Excellence in Brain Science and Intelligence Technology, Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
  • 6 University of Chinese Academy of Sciences, Beijing, China.
  • 7 Laboratory of Human Virology and Oncology, Shantou University Medical College, Shantou, China.
PMID: 38626263 DOI: 10.1371/journal.ppat.1012141
Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) is a double-stranded DNA virus etiologically associated with multiple malignancies. Both latency and sporadic lytic reactivation contribute to KSHV-associated malignancies, however, the specific roles of many KSHV lytic gene products in KSHV replication remain elusive. In this study, we report that ablation of ORF55, a late gene encoding a tegument protein, does not impact KSHV lytic reactivation but significantly reduces the production of progeny virions. We found that cysteine 10 and 11 (C10 and C11) of pORF55 are palmitoylated, and the palmytoilation is essential for its Golgi localization and secondary envelope formation. Palmitoylation-defective pORF55 mutants are unstable and undergo proteasomal degradation. Notably, introduction of a putative Golgi localization sequence to these palmitoylation-defective pORF55 mutants restores Golgi localization and fully reinstates KSHV progeny virion production. Together, our study provides new insight into the critical role of pORF55 palmitoylation in KSHV progeny virion production and offers potential therapeutic targets for the treatment of related malignancies.

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