Amino Acid Deletions in p6Gag Domain of HIV-1 CRF07_BC Ameliorate Galectin-3 Mediated Enhancement in Viral Budding

Int J Mol Sci. 2020 Apr 21;21(8):2910. doi: 10.3390/ijms21082910.

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.

Keywords: Alix; CRF07_BC; Galectin-3; HIV-1; p6Gag.

MeSH terms

  • Adolescent
  • Adult
  • CD4 Lymphocyte Count
  • Cell Line
  • Female
  • 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
  • gag Gene Products, Human Immunodeficiency Virus / genetics*
  • gag Gene Products, Human Immunodeficiency Virus / metabolism*

Substances

  • Galectin 3
  • gag Gene Products, Human Immunodeficiency Virus
  • p6 gag protein, Human immunodeficiency virus 1