Abstract
HIV-1 CRF07_BC is a recombinant virus with amino acid (a.a.) deletions in p6Gag, 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 p6Gag (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 (p < 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 (p < 0.05), while the promoting effect was ameliorated in CRF07_BC-7d. Co-immunoprecipitation found that deletions in the p6Gag reduced Gal-3-mediated enhancement of the Alix–Gag interaction.
Highlights
HIV-1 CRF07_BC is a recombinant of the B and C subtypes of the HIV-1 virus
Results indicated that expression of galectin-3 led to a significant rise in the levels of Alix co-precipitated with Gag in pCRF07_BC-wt-transfected cells (p < 0.05) (Figure 5B), but the galectin-3-mediated enhancement was not noted in the pCRF07_BC-7d-transfected group (p > 0.05) (Figure 5C). These results indicated that galectin-3 was dependent on Alix to interact with Gag, and that amino acid deletions in the p6Gag reduced the galectin-3-mediated promotion of the Alix–Gag association
We evaluated the characterization of HIV-1 CRF07_BC from our cohort in Taiwan, as well as the potential role that galectin-3 plays in HIV-1 CRF07_BC infection
Summary
HIV-1 CRF07_BC is a recombinant of the B (the Thailand variant of subtype B) and C subtypes of the HIV-1 virus. The Pr55gag polyprotein is translated and further cleaved into matrix protein (p17; MA), capsid protein (p24; CA), p2, nucleocapsid protein (P7; NC), p1, and p6gag. Tsg101 and Alix are primarily associated with endosomal sorting complex required for transport (ESCRT). They are important for the recognition of modified membrane proteins due to ubiquitination and the sorting of cargoes into membrane domains for the formation of the intralumenal vesicles (ILVs) of multivesicular bodies [13]. Knockdown or blocking of the interaction between Tsg101 or Alix with p6Gag were reported to ameliorate HIV viral assembly and budding [14,15,16]
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