CRISPR Screen of Druggable Targets in Small Cell Lung Cancer Identified ATM Inhibitor (AZD1390) as a Radiosensitizer.

Purpose: Small cell lung cancer (SCLC) is an aggressive and lethal form of lung cancer and the overall 5-year survival (OS) for patients is a dismal 7%. Radiation therapy (RT) provides some benefit for selected patients with SCLC but could be improved with radiosensitizing agents. In this study, we identified novel radiosensitizers for SCLC by a CRISPR-Cas9 screen and evaluated the efficacy of ATM inhibitor AZD1390 as a radiosensitizer of SCLC.

SARS-CoV-2 impairs interferon production via NSP2-induced repression of mRNA translation.

Viruses evade the innate immune response by suppressing the production or activity of cytokines such as type I interferons (IFNs). Here we report the discovery of a mechanism by which the SARS-CoV-2 virus coopts an intrinsic cellular machinery to suppress the production of the key immunostimulatory cytokine IFN-β. We reveal that the SARS-CoV-2 encoded nonstructural protein 2 (NSP2) directly interacts with the cellular GIGYF2 protein.

PARP inhibitors for small cell lung cancer and their potential for integration into current treatment approaches.

Small cell lung cancer (SCLC) is a very aggressive, highly lethal, neuroendocrine tumor that constitutes 15% of all lung cancer cases. It is characterized by its rapid disease progression and high relapse rate leading to poor survival for diagnosed patients. Recently, poly (ADP-ribose) polymerase inhibitors (PARPi) have emerged as a novel therapeutic strategy for SCLC.

Characterization of the Role of Host Cellular Factor Histone Deacetylase 10 during HIV-1 Replication.

To date, a series of histone deacetylases have been documented to restrict HIV-1 replication at different steps. In this study, we identified histone deacetylase 10 (HDAC10) as an inhibitory factor against HIV-1 replication. Our results showed that endogenous HDAC10 is downregulated at the transcriptional level during HIV-1 replication.

HIV-1 envelope glycoprotein stimulates viral transcription and increases the infectivity of the progeny virus through the manipulation of cellular machinery.

During HIV infection, large amounts of progeny viral particles, including infectious virus and a large proportion of defective viral particles, are produced. Despite of the critical role of the infectious viruses in infection and pathogenesis in vivo, whether and how those defective viral particles, especially the virus-associated envelope glycoprotein (vEnv), would impact viral infection remains elusive. In this study, we investigated the effect of vEnv on HIV-infected T cells and demonstrated that the vEnv was able to stimulate HIV transcription in HIV-infected cells, including peripheral blood mononuclear cells (PBMCs) isolated from HIV patients.

Apobec3G-Based Strategies to Defeat HIV Infection.

Background: To suppress HIV infection, host cells have evolved numerous defenses that generally belong to the innate and adaptive immune responses. Over the last decade, extensive efforts have been focused on understanding HIV restriction factors and mechanisms of evasion. The host protein APOBEC3G (A3G) was identified as a member of cytidine deaminase family in 2002, and it was shown that, in the absence of HIV encoded Vif, A3G can block the replication of HIV-1 by introducing viral hypermutations during reverse transcription, also conferring innate immunity to the virus.

Characterization of the inhibitory effect of an extract of Prunella vulgaris on Ebola virus glycoprotein (GP)-mediated virus entry and infection.

Currently, no approved antiviral therapeutic is available for treatment or prevention of Ebola virus (EBOV) infection. In this study, we characterized an EBOV-glycoprotein (GP) pseudotyped HIV-1-based vector system in different cell cultures, including human umbilical vein endothelial cells (HUVECs) and human macrophages, for the screening of anti-EBOV-GP agent(s). Based on this system, we demonstrated that an aqueous extract (CHPV) from the Chinese herb Prunella vulgaris displayed a potent inhibitory effect on EBOV-GP pseudotyped virus (EBOV-GP-V)-mediated infection in various cell lines, including HUVEC and macrophage.

White spot syndrome virus IE1 and WSV056 modulate the G1/S transition by binding to the host retinoblastoma protein.

DNA viruses often target cellular proteins to modulate host cell cycles and facilitate viral genome replication. However, whether proliferation of white spot syndrome virus (WSSV) requires regulation of the host cell cycle remains unclear. In the present study, we show that two WSSV paralogs, IE1 and WSV056, can interact with Litopenaeus vannamei retinoblastoma (Rb)-like protein (lv-RBL) through the conserved LxCxE motif.