HIV-1 replication in cell lines harboring INI1/hSNF5 mutations.

Area of Science:

• Virology
• Molecular Biology
• Oncology

Background:

• INI1/hSNF5 is a cellular protein interacting with HIV-1 integrase (IN) and incorporated into virions.
• INI1 is a tumor suppressor, with mutations found in malignant rhabdoid tumors.
• INI1 is associated with pre-integration and reverse transcription complexes.

Purpose of the Study:

• To assess the effect of INI1 on HIV-1 replication using INI1-deficient malignant rhabdoid tumor cell lines.
• To investigate the role of INI1 in HIV-1 particle production, infectivity, and reverse transcription.

Main Methods:

• Utilized malignant rhabdoid tumor cell lines (MON and STA-WT1) with INI1 mutations.
• Assessed HIV-1 particle production, transduction efficiency, and infectivity in INI1-deficient cells.
• Reintroduced INI1 into cell lines to evaluate rescue effects.
• Analyzed reverse transcription products and exogenous reverse transcriptase activity.

Main Results:

• HIV-1 particle production was severely reduced in INI1-deficient cells (MON and STA-WT1).
• Reintroduction of INI1 enhanced particle production.
• HIV-1 produced in MON cells showed reduced infectivity and defective early/late reverse transcription, with no INI1 detected in virions.
• HIV-1 produced in STA-WT1 cells had normal infectivity, with INI1 detected in virions.

Conclusions:

• INI1-deficient cells exhibit reduced HIV-1 particle production, partially restored by INI1 reintroduction.
• HIV-1 infectivity is affected in some INI1-defective cells, potentially correlating with INI1 presence in virions.
• A block in early reverse transcription events occurs in MON cells, suggesting INI1's importance for this stage.