Non-thermal plasma modulates cellular markers associated with immunogenicity in a model of latent HIV-1 infection

Effective control of infection by human immunodeficiency virus type 1 (HIV-1), the causative agent of the acquired immunodeficiency syndrome (AIDS), requires continuous and life-long use of anti-retroviral therapy (ART) by people living with HIV-1 (PLWH). In the absence of ART, HIV-1 reemergence from latently infected cells is ineffectively suppressed due to suboptimal innate and cytotoxic T lymphocyte responses. However, ART-free control of HIV-1 infection may be possible if the inherent immunological deficiencies can be reversed or restored. Herein we present a novel approach for modulating the immune response to HIV-1 that involves the use of non-thermal plasma (NTP), which is an ionized gas containing various reactive oxygen and nitrogen species (RONS). J-Lat cells were used as a model of latent HIV-1 infection to assess the effects of NTP application on viral latency and the expression of pro-phagocytic and pro-chemotactic damage-associated molecular patterns (DAMPs). Exposure of J-Lat cells to NTP resulted in stimulation of HIV-1 gene expression, indicating a role in latency reversal, a necessary first step in inducing adaptive immune responses to viral antigens. This was accompanied by the release of pro-inflammatory cytokines and chemokines including interleukin-1β (IL-1β) and interferon-γ (IFN-γ); the display of pro-phagocytic markers calreticulin (CRT), heat shock proteins (HSP) 70 and 90; and a correlated increase in macrophage phagocytosis of NTP-exposed J-Lat cells. In addition, modulation of surface molecules that promote or inhibit antigen presentation was also observed, along with an altered array of displayed peptides on MHC I, further suggesting methods by which NTP may modify recognition and targeting of cells in latent HIV-1 infection. These studies represent early progress toward an effective NTP-based ex vivo immunotherapy to resolve the dysfunctions of the immune system that enable HIV-1 persistence in PLWH.

Keywords

cell marker, gamma interferon, heat shock protein 70, heat shock protein 90, high mobility group B1 protein, interleukin 1beta, reactive nitrogen species, reactive oxygen metabolite, virus antigen, antiretrovirus agent, apoptosis, Article, CD8+ T lymphocyte, cell culture, cell mediated cytotoxicity, cell phagocytosis, cell surface, controlled study, cytokine release, gene expression, Human immunodeficiency virus 1 infection, immune deficiency, immune response, immunogenicity, immunomodulation, immunopathology, immunotherapy, in vitro study, J-Lat 5A8 cell line, Jurkat cell, line, latent virus infection, ligand binding, macrophage, major histocompatibility complex, mass spectrometry, nonhuman, phagocyte, plasma gas, protein database, protein isolation, target cell, THP-1 cell line, upregulation, virus gene, virus genome, virus latency, Western blotting, acquired immune deficiency syndrome, CD4+ T lymphocyte, drug effect, human, Human immunodeficiency virus 1, Human immunodeficiency virus infection, immunity, immunology, lymphocyte activation, metabolism, pathogenicity, physiology, plasma gas, virus activation, virus replication, Acquired Immunodeficiency Syndrome, Anti-Retroviral Agents, CD4-Positive T-Lymphocytes, HIV Infections, HIV-1, Humans, Immunity, Jurkat Cells, Lymphocyte Activation, THP-1 Cells, Virus Activation, Virus Latency, Virus Replication

URI

https://oa.tib.eu/renate/handle/123456789/8612
https://doi.org/10.34657/7650

Citation

Mohamed, H., Clemen, R., Freund, E., Lackmann, J.-W., Wende, K., Connors, J., et al. (2021). Non-thermal plasma modulates cellular markers associated with immunogenicity in a model of latent HIV-1 infection. 16(3). https://doi.org//10.1371/journal.pone.0247125

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CC BY 4.0 Unported

https://creativecommons.org/licenses/by/4.0/

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