Amino Acid Deletions in p6 Gag Domain of HIV-1 CRF07_BC Ameliorate Galectin-3 Mediated Enhancement in Viral Budding

• Published in: International journal of molecular sciences Vol. 21; no. 8
• Main Authors: Wang, Wen-Hung, Yeh, Chun-Sheng, Lin, Chih-Yen, Yuan, Ruei-Yu, Urbina, Aspiro Nayim, Lu, Po-Liang, Chen, Yen-Hsu, Chen, Yi-Ming Arthur, Liu, Fu-Tong, Wang, Sheng-Fan
• Format: Journal Article
• Language: English
• Published: Switzerland 21.04.2020
• Subjects: Adolescent; Adult; CD4 Lymphocyte Count; Cell Line; Female; gag Gene Products, Human Immunodeficiency Virus - genetics; gag Gene Products, Human Immunodeficiency Virus - metabolism; Galectin 3 - blood; Galectin 3 - metabolism; HIV Infections - immunology; HIV Infections - metabolism; HIV Infections - virology; HIV-1 - physiology; Host-Pathogen Interactions; Humans; Male; Middle Aged; Models, Biological; Sequence Deletion; Viral Load; Virus Release; Young Adult; HIV-1; p6Gag; Alix; Galectin-3; CRF07_BC

HIV-1 CRF07_BC is a recombinant virus with amino acid (a.a.) deletions in p6 , which are overlapped with the Alix-binding domain. Galectin-3 (Gal3), a β-galactose binding lectin, has been reported to interact with Alix and regulate HIV-1 subtype B budding. This study aims to evaluate the role of Gal3 in HIV-1 CRF07_BC infection and the potential effect of a.a. deletions on Gal3-mediated regulation. A total of 38 HIV-1+ injecting drug users (IDUs) were enrolled in the study. Viral characterization and correlation of Gal3 were validated. CRF07_BC containing 7 a.a. deletions and wild-type in the p6 (CRF07_BC-7d and -wt) were isolated and infectious clones were generated. Viral growth kinetic and budding assays using Jurkat-CCR5/Jurkat-CCR5-Gal3 cells infected with CRF07_BC were performed. Results indicate that 69.4% (25/38) of the recruited patients were identified as CRF07_BC, and CRF07_BC-7d was predominant. Slow disease progression and significantly higher plasma Gal3 were noted in CRF07_BC patients ( < 0.01). Results revealed that CRF07_BC infection resulted in Gal3 expression, which was induced by Tat. Growth dynamic and budding assays indicated that Gal3 expression in Jurkat-CCR5 cells significantly enhanced CRF07_BC-wt replication and budding ( < 0.05), while the promoting effect was ameliorated in CRF07_BC-7d. Co-immunoprecipitation found that deletions in the p6 reduced Gal-3-mediated enhancement of the Alix-Gag interaction.