Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
1.
J Virol ; 97(10): e0039623, 2023 10 31.
Article in English | MEDLINE | ID: mdl-37706687

ABSTRACT

IMPORTANCE: This study highlights the crucial role RNA processing plays in regulating viral gene expression and replication. By targeting SR kinases, we identified harmine as a potent inhibitor of HIV-1 as well as coronavirus (HCoV-229E and multiple SARS-CoV-2 variants) replication. Harmine inhibits HIV-1 protein expression and reduces accumulation of HIV-1 RNAs in both cell lines and primary CD4+ T cells. Harmine also suppresses coronavirus replication post-viral entry by preferentially reducing coronavirus sub-genomic RNA accumulation. By focusing on host factors rather than viral targets, our study offers a novel approach to combating viral infections that is effective against a range of unrelated viruses. Moreover, at doses required to inhibit virus replication, harmine had limited toxicity and minimal effect on the host transcriptome. These findings support the viability of targeting host cellular processes as a means of developing broad-spectrum anti-virals.


Subject(s)
Antiviral Agents , Coronavirus , HIV-1 , Harmine , Humans , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Coronavirus/drug effects , Coronavirus/physiology , Coronavirus Infections/drug therapy , Harmine/pharmacology , Harmine/therapeutic use , HIV-1/drug effects , HIV-1/physiology , Virus Replication/drug effects
2.
Cell Host Microbe ; 29(3): 435-447.e9, 2021 03 10.
Article in English | MEDLINE | ID: mdl-33571449

ABSTRACT

Natural killer (NK) cells are innate cytolytic effectors that target HIV-infected CD4+ T cells. In conjunction with antibodies recognizing the HIV envelope, NK cells also eliminate HIV-infected targets through antibody-dependent cellular cytotoxicity (ADCC). However, how these NK cell functions impact infected macrophages is less understood. We show that HIV-infected macrophages resist NK cell-mediated killing. Compared with HIV-infected CD4+ T cells, initial innate NK cell interactions with HIV-infected macrophages skew the response toward cytokine production, rather than release of cytolytic contents, causing inefficient elimination of infected macrophages. Studies with chimeric antigen receptor (CAR) T cells demonstrate that the viral envelope is equally accessible on CD4+ T cells and macrophages. Nonetheless, ADCC against macrophages is muted compared with ADCC against CD4+ T cells. Thus, HIV-infected macrophages employ mechanisms to evade immediate cytolytic NK cell function while preserving inflammatory cytokine responses. These findings emphasize the importance of eliminating infected macrophages for HIV cure efforts.


Subject(s)
Cytokines/metabolism , HIV Infections/immunology , Killer Cells, Natural/immunology , Macrophages/virology , Antibody-Dependent Cell Cytotoxicity , CD4-Positive T-Lymphocytes/immunology , HIV Antibodies/immunology , HIV-1 , Humans
SELECTION OF CITATIONS
SEARCH DETAIL
...