determining-3-termini-sequences-nascent-single-stranded-viral-dna

Determining 3'-Termini and Sequences of Nascent Single-Stranded Viral DNA Molecules during HIV-1 Reverse Transcription in Infected Cells

Monitoring of nucleic acid intermediates during virus replication provides insights into the effects and mechanisms of action of antiviral compounds and ...

King's College London

Interferons (IFNs) mediate cellular defence against viral pathogens by upregulation of IFN-stimulated genes whose products interact with viral components or alter cellular physiology to suppress viral replication. Among the IFN-stimulated genes that can inhibit influenza A virus (IAV) are the myxovirus resistance 1 GTPase and IFN-induced transmembrane protein 3 (refs ). Here, we use ectopic expression and gene knockout to demonstrate that the IFN-inducible 219-amino acid short isoform of human nuclear receptor coactivator 7 (NCOA7) is an inhibitor of IAV as well as other viruses that enter the cell by endocytosis, including hepatitis C virus. NCOA7 interacts with the vacuolar H-ATPase (V-ATPase) and its expression promotes cytoplasmic vesicle acidification, lysosomal protease activity and the degradation of endocytosed antigen. Step-wise dissection of the IAV entry pathway demonstrates that NCOA7 inhibits fusion of the viral and endosomal membranes and subsequent nuclear translocation of viral ribonucleoproteins. Therefore, NCOA7 provides a mechanism for immune regulation of endolysosomal physiology that not only suppresses viral entry into the cytosol from this compartment but may also regulate other V-ATPase-associated cellular processes, such as physiological adjustments to nutritional status, or the maturation and function of antigen-presenting cells.

The interferon-inducible isoform of NCOA7 inhibits endosome-mediated viral entry.

APOBEC restriction goes nuclear.

In the version of Supplementary Fig. 5a originally published with this Letter, the authors mistakenly duplicated images of LAMP1 staining in place of CD63 staining; this has now been amended to the correct version shown below.

Michael H. Malim

Department of Infectious Diseases,
School of Immunology & Microbial Sciences,
Department of Infectious Diseases, School of Immunology & Microbial Sciences

King's College London

Determining 3'-Termini and Sequences of Nascent Single-Stranded Viral DNA Molecules during HIV-1 Reverse Transcription in Infected Cells

Michael H. Malim

Department of Infectious Diseases,School of Immunology & Microbial Sciences,Department of Infectious Diseases, School of Immunology & Microbial Sciences

King's College London

Determining 3'-Termini and Sequences of Nascent Single-Stranded Viral DNA Molecules during HIV-1 Reverse Transcription in Infected Cells

Department of Infectious Diseases,
School of Immunology & Microbial Sciences,
Department of Infectious Diseases, School of Immunology & Microbial Sciences