Related Experiment Video
Updated: Mar 13, 2026
Isolation, Transfection, and Culture of Primary Human Monocytes
Published on: December 16, 2019
SARS-CoV-2-Induced Macrophage Polarization Reverses HIV-1 Latency in J-Lat Cells Through TNFα Signaling
Patricio Jarmoluk1, Franco Agustín Sviercz1, Cintia Cevallos1
1Viral Immunopathology Laboratory, Institute for Biomedical Research on Retroviruses and AIDS (INBIRS), National Scientific and Technical Research Council (CONICET), University of Buenos Aires (UBA), Buenos Aires, Argentina, uba.ar.
Insights
SARS-CoV-2 infection can indirectly reactivate latent HIV in lymphoid cells by triggering pro-inflammatory cytokines from infected macrophages. This highlights potential therapeutic strategies targeting cytokine signaling to manage HIV reactivation during COVID-19 coinfection.
Area of Science:
- Virology
- Immunology
- Infectious Diseases
Background:
- Coronavirus disease 2019 (COVID-19) may impact human immunodeficiency virus (HIV)-1 progression in people living with HIV (PLWH).
- The potential for SARS-CoV-2 to influence HIV reactivation in latently infected cells requires investigation, even in individuals on combined antiretroviral therapy (cART).
Purpose of the Study:
- To investigate whether SARS-CoV-2 infection influences HIV reactivation in latently infected lymphoid cells.
- To explore the mechanisms by which SARS-CoV-2 might affect HIV latency.
Main Methods:
- Utilized J-Lat cells (HIV-infected lymphoid cells in latency) for latency reversal assays.
- Stimulated cells with phorbol 12-myristate 13-acetate (PMA), SARS-CoV-2, or conditioned media (CM) from M1/M2 polarized macrophages infected with SARS-CoV-2 variants.
- Assessed HIV latency reversal, cytokine release (TNFα, IL-10), reactive oxygen species (ROS), and macrophage polarization using flow cytometry, RT-qPCR, and ELISA.
Main Results:
- SARS-CoV-2 did not directly infect or reactivate HIV in J-Lat cells due to low ACE2 expression.
- Conditioned media from SARS-CoV-2-infected M1 macrophages significantly reactivated latent HIV, primarily driven by TNFα release.
- Prolonged SARS-CoV-2 exposure induced an M2 macrophage phenotype, releasing IL-10 and reducing latency reactivation.
Conclusions:
- SARS-CoV-2 indirectly reverses HIV latency by promoting pro-inflammatory cytokine release from infected macrophages.
- Findings suggest therapeutic strategies involving cytokine modulation to prevent HIV reactivation during SARS-CoV-2 coinfection.
- Controlling inflammation and immune dysregulation is crucial for managing coinfected individuals.
Introduction:
Coronavirus disease 2019 (COVID-19) may have both short- and long-term impacts on the progression of human immunodeficiency virus (HIV)-1 after acute SARS-CoV-2 infection in people living with HIV (PLWH), even those on combined antiretroviral therapy (cART). This study aimed to investigate whether SARS-CoV-2 could influence HIV reactivation in latently infected lymphoid cells.
Methods:
HIV-infected lymphoid (J-Lat) cells, characterized by proviral latency under unstimulated conditions, were used for latency reversal assays with phorbol 12-myristate 13-acetate (PMA), free SARS-CoV-2 particles, or conditioned media (CM) from macrophages. Monocytes isolated from donor blood were differentiated into macrophages (monocyte-derived macrophages [MDMs]) and polarized to M1 or M2 phenotypes before stimulation or with two SARS-CoV-2 variants (wild-type and BA.5) infection. Additionally, the effects of redox imbalance on latency reversal in both J-Lat and myeloid (U1) latency models were measured. SARS-CoV-2 RNA was quantified by RT-qPCR targeting ORF1ab and N genes, and latency reversal and reactive oxygen species (ROS) levels were assessed by flow cytometry. TNFα involvement was confirmed through neutralization assays, while cytokines and polarization markers were analyzed via ELISA and fluorescent antibodies.
Results:
Jurkat and J-Lat cells had low ACE2 expression and were not permissive to SARS-CoV-2 infection. SARS-CoV-2 exposure alone did not induce HIV latency reversal in J-Lat cells. However, CM from M1-polarized, resiquimod (R-848)-treated, and SARS-CoV-2-infected macrophages significantly reactivated latent HIV. TNFα was identified as the primary driver of latency reversal, with no significant changes in ROS levels. Prolonged SARS-CoV-2 exposure shifted macrophage polarization toward an anti-inflammatory M2 phenotype, characterized by IL-10 release, which reduced latency reactivation.
Conclusions:
This study demonstrates that SARS-CoV-2 can indirectly reverse HIV latency in lymphoid cells by promoting the release of pro-inflammatory cytokines from infected macrophages. These findings suggest potential therapeutic strategies for preventing HIV reactivation during SARS-CoV-2 coinfection, emphasizing the modulation of cytokine signaling to control inflammation while minimizing immune dysregulation.
