HLA-C is necessary for optimal human immunodeficiency virus type 1 infection of human peripheral blood CD4 lymphocytes

Area of Science:

• Immunology
• Virology
• Molecular Biology

Background:

• Previous hypotheses suggested that open conformers of Human Leukocyte Antigen (HLA)-C on target cells influence human immunodeficiency virus (HIV) infectability.
• Monoclonal antibody (mAb) L31 specifically targets HLA-C open conformers, enabling investigation of their role in HIV entry.

Purpose of the Study:

• To confirm the physiological relevance of HLA-C's role in HIV infectability using small interfering RNA (siRNA) technology.
• To investigate the impact of silenced HLA-C expression on HIV infectability in primary human cells.

Main Methods:

• Silencing HLA-C expression in peripheral blood lymphocytes (PBLs) from healthy donors using siRNA technology.
• Assessing HIV infectability using various HIV strains (IIIB, Bal, primary isolates) and pseudoviruses in silenced and control cells.
• Utilizing HLA-C-positive and -negative cell lines for additional confirmation.

Main Results:

• HIV infectability was significantly reduced (P=0.016) in siRNA-silenced PBLs compared to control cells in 10 out of 11 donors.
• Restoration of normal infectability correlated with the waning of siRNA interference and recovery of HLA-C expression.
• Pseudoviruses with env genes from specific HIV strains showed even greater differences in infection rates on silenced lymphocytes.

Conclusions:

• HLA-C expression plays a significant role in modulating target cell infectability by human immunodeficiency virus (HIV).
• Silencing HLA-C expression provides a method to reduce HIV entry into host cells.
• These findings highlight HLA-C as a potential factor influencing HIV pathogenesis and therapeutic strategies.