Integration of the DNA copy of HIV-1 genome into the cellular genome results in series of damages, repair of which is critical for successful replication of the virus. We have previously demonstrated that the ATM and DNA-PK kinases, normally responsible for repairing double-strand breaks in the cellular DNA, are required to initiate the HIV-1 DNA postintegrational repair, even though integration does not result in DNA double-strand breaks. In this study, we analyzed changes in phosphorylation status of ATM (pSer1981), DNA-PK (pSer2056), and their related kinase ATR (pSer428), as well as their targets: Chk1 (pSer345), Chk2 (pThr68), H2AX (pSer139), and p53 (pSer15) during the HIV-1 DNA postintegrational repair. We have shown that ATM and DNA-PK, but not ATR, undergo autophosphorylation during postintegrational DNA repair and phosphorylate their target proteins Chk2 and H2AX. These data indicate common signaling mechanisms between the double-strand DNA break repair and postintegrational repair of HIV-1 DNA.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1134/S0006297924060117 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Ritonavir enhances the efficacy of amprenavir: a promising combination therapy by targeting Leishmania DNA Topoisomerase I for treatment of visceral leishmaniasis HIV-VL co-infection.
Exp Parasitol
January 2025
Department of Biotechnology, Savitribai Phule Pune University, Pune-411007, India. Electronic address:
Visceral leishmaniasis (VL) is an opportunistic infection in HIV patients with higher relapse and mortality rate. The number of HIV-VL patients is comparatively higher in areas where both infections are endemic. However, the conventional chemotherapeutic agents have limited success due to drug toxicity, efficacy variance and overall cost of treatment.
View Article and Find Full Text PDFAnatomical, subset, and HIV-dependent expression of viral sensors and restriction factors.
Cell Rep
January 2025
Gladstone Institutes, San Francisco, CA, USA; Department of Urology, UCSF, San Francisco, CA, USA. Electronic address:
We developed viral sensor and restriction factor-cytometry by time of flight (VISOR-CyTOF), which profiles 19 viral sensors and restriction factors (VISORs) simultaneously in single cells, and applied it to 41 postmortem tissues from people with HIV. Mucosal myeloid cells are well equipped with SAMHD1 and sensors of viral capsid and DNA while CD4 T cells are not. In lymph node CD4 Tfh, VISOR expression patterns reflect those favoring integration but blocking HIV gene expression, thus favoring viral latency.
View Article and Find Full Text PDFStructure-switchable branched inhibitors regulate the activity of CRISPR-Cas12a for nucleic acid diagnostics.
Anal Chim Acta
January 2025
Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, People's Republic of China; Wuhan Research Center for Infectious Diseases and Cancer, Chinese Academy of Medical Sciences, Wuhan, People's Republic of China; Hubei Engineering Center for Infectious Disease Prevention, Control and Treatment, Wuhan, People's Republic of China. Electronic address:
Background: In current years, the CRISPR (clustered regularly interspaced short palindromic repeats) based strategies have emerged as the most promising molecular tool in the field of gene editing, intracellular imaging, transcriptional regulation and biosensing. However, the recent CRISPR-based diagnostic technologies still require the incorporation of other amplification strategies (such as polymerase chain reaction) to improve the cis/trans cleavage activity of Cas12a, which complicates the detection workflow and lack of a uniform compatible system to respond to the target in one pot.
Results: To better fully-functioning CRISPR/Cas12a, we reported a novel technique for straightforward nucleic acid detection by incorporating enzyme-responsive steric hindrance-based branched inhibitors with CRISPR/AsCas12a methodology.
Novel rhesus macaque immunoglobulin germline genes identified by three sequencing approaches.
Front Immunol
January 2025
Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, United States.
Introduction: Rhesus macaques have long been a focus of research for understanding immune responses to human pathogens due to their close phylogenetic relationship with humans. As rhesus macaque antibody germlines show high degrees of polymorphism, the spectrum of database-covered genes expressed in individual macaques remains to be determined.
Methods: Here, four rhesus macaques infected with SHIV became a study of interest because they developed broadly neutralizing antibodies against HIV-1.
HIV Replication Under High-Level Cabotegravir Is Associated with the Appearance of 3'-PPT Mutations, Circular DNA Transcription and Recombination.
Viruses
November 2024
Laboratory Branch, Division of HIV Prevention, National Center for HIV, Viral Hepatitis, STD and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.
The HIV integrase inhibitor, dolutegravir (DTG), in the absence of eliciting integrase (int) resistance, has been reported to select mutations in the virus 3'-polypurine tract (3'-PPT) adjacent to the 3'-LTR U3. An analog of DTG, cabotegravir (CAB), has a high genetic barrier to drug resistance and is used in formulations for treatment and long-acting pre-exposure prophylaxis. We examined whether mutations observed for DTG would emerge in vitro with CAB.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!