Significance Antiretroviral therapy cannot eradicate HIV-1 because the virus can become transcriptionally inactive in resting memory CD4+ T cells (and other cell types), which are long-lived, thus generating a reservoir undetectable by the immune system. When therapy is stopped, the latent viral reservoir is activated and HIV-1 rebounds. Our understanding of HIV-1 latency and reactivation is incomplete. Here we report that the heat shock protein 90 (Hsp90) regulates HIV-1 reactivation from latency by controlling the NF-kB pathway. Therefore Hsp90 is a key molecule linking HIV-1 reactivation from latency to CD4+ T-cell activation. Selective Hsp90 inhibitors combined with PKC-ϑ inhibitors, all in phase II clinical trials, potently suppressed HIV-1 reactivation, thus Hsp90 may be a novel target to control HIV-1 latency.

Flaviviruses are a major cause of disease in humans and animals worldwide. Tick-borne encephalitis virus (TBEV) is the most important arthropod-borne flavivirus endemic in Europe and is the etiological agent of tick-borne encephalitis, a potentially fatal infection of the central nervous system. However, the contributions of host proteins during TBEV infection are poorly understood. In this work, we investigate the cellular protein TIA-1 and its cognate factor TIAR, which are stress-induced RNA

The activity of the cyclin‐dependent kinase 9 (CDK9) is critical for HIV‐1 Tat‐mediated transcription and represents a promising target for antiviral therapy. Here we present computational studies that, along with preliminary synthetic efforts, allowed us to identify and characterize a new class of nontoxic anti‐CDK9 chemotypes based on the 2‐phenylquinazolinone scaffold. Inhibition of CDK9 translated into the ability to interfere selectively with Tat‐mediated transactivation of the viral promoter and in the inhibition of HIV‐1 reactivation from latently infected cells, with the most potent derivative 37 (2‐(4‐aminophenyl)‐7‐chloroquinazolin‐4(3H)‐one) showing an IC50 value of 4.0 μM. Because the herein reported 2‐phenylquinazolinones are merely fragments, they are largely optimizable, paving the way to derivatives with improved potency.

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