Increased susceptibility of differentiated mononuclear phagocytes to productive infection with human immunodeficiency virus-1 (HIV-1)

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• Human immunodeficiency virus type 1 (HIV-1) infects mononuclear phagocytes.
• Susceptibility of different mononuclear phagocyte subsets to HIV-1 infection is not fully understood.
• Alveolar macrophages (AM) and cultured monocytes (CM) are key cells in the lung immune response.

Purpose of the Study:

• To compare the susceptibility of freshly isolated blood monocytes (MN), cultured monocytes (CM), and alveolar macrophages (AM) to productive HIV-1 infection.
• To investigate the mechanisms underlying differential HIV-1 susceptibility in these cell types.

Main Methods:

• Primary human monocytes (MN), in vitro differentiated monocytes (CM), and alveolar macrophages (AM) were isolated from healthy donors.
• Cells were infected with the macrophage-tropic HIV-1 strain HIV-1JR-FL.
• Viral replication was assessed by measuring p24 gag antigen levels using ELISA.
• Viral DNA levels, including entry and reverse transcription, were analyzed by quantitative PCR.

Main Results:

• Freshly isolated MN showed negligible HIV-1 replication (p24 antigen).
• AM exhibited significant HIV-1 replication (peak 4145 pg/ml), and CM showed higher replication (peak 9216 pg/ml).
• Quantitative PCR indicated that differences in viral entry, not reverse transcription completion, contribute to varied virus production.

Conclusions:

• Alveolar macrophages and cultured monocytes are significantly more susceptible to productive HIV-1 infection than freshly isolated blood monocytes.
• Increased susceptibility of AM to HIV-1 may contribute to the pathogenesis of lung disorders in acquired immunodeficiency syndrome (AIDS).
• Understanding these cellular differences is crucial for managing HIV-1-associated pulmonary complications.