HIV-1 virion fusion assay: uncoating not required and no effect of Nef on fusion

Virology
Marielle CavroisWarner C Greene

Abstract

We recently described a sensitive and specific assay that detects the fusion of HIV-1 virions to a broad range of target cells, including primary CD4 cells. This assay involves the use of virions containing beta-lactamase-Vpr (BlaM-Vpr) and the loading of target cells with CCF2, a fluorogenic substrate of beta-lactamase. Since Vpr strongly associates with the viral core, uncoating of the viral particle might be required for effective cleavage of CCF2 by BlaM-Vpr. Here, we show that BlaM-Vpr within mature viral cores effectively cleaves CCF2, indicating that this assay measures virion fusion independently of uncoating. We also show that wildtype and Nef-deficient HIV-1 virions fuse with equivalent efficiency to HeLa-CD4 cells, SupT1 T cells, and primary CD4 T cells. Since Nef enhances cytoplasmic delivery of viral cores and increases viral infectivity, these findings indicate that Nef enhances an early post-fusion event in the multistep process of viral entry. Possible sites of Nef action include enlargement of the fusion pore, enhanced uncoating of viral particles, and more efficient passage of viral cores through the dense cortical actin network located immediately beneath the plasma membrane.

References

Mar 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·M K GornyS Zolla-Pazner
Nov 24, 1994·Nature·E K FrankeJ Luban
Oct 6, 1997·Proceedings of the National Academy of Sciences of the United States of America·A A BukovskyH G Göttlinger
Nov 17, 1998·The Journal of Cell Biology·Y JenkinsW C Greene
Jun 8, 1999·Annual Review of Immunology·E A BergerJ M Farber
Aug 23, 2001·Current Biology : CB·Y H ZhengB M Peterlin
Mar 7, 2002·Microbes and Infection·Vivek K AroraJ Victor Garcia
Jul 2, 2002·Nature Medicine·Warner C Greene, B Matija Peterlin
Oct 2, 2002·Nature Biotechnology·Marielle CavroisWarner C Greene
Jun 26, 2003·Proceedings of the National Academy of Sciences of the United States of America·Yong-Hui ZhengB Matija Peterlin
Aug 2, 2003·Molecular Membrane Biology·Satinder S RawatAnu Puri
Sep 13, 2003·Journal of Virology·Minoru TobiumeChristopher Aiken
Sep 24, 2004·Virology·Marielle CavroisWarner C Greene

❮ Previous
Next ❯

Citations

Aug 22, 2008·Journal of Virology·Massimo PizzatoHeinrich G Göttlinger
Nov 7, 2008·Journal of Virology·Nadine LaguetteStéphane Basmaciogullari
May 5, 2010·Proceedings of the National Academy of Sciences of the United States of America·Massimo Pizzato
Oct 9, 2012·The Journal of Biological Chemistry·Robert BlumenthalMathias Viard
May 10, 2011·Chemical Society Reviews·Andrew RazgulinJianghong Rao
Jul 3, 2010·Molecular Aspects of Medicine·Nadine LaguetteStéphane Basmaciogullari
Apr 3, 2007·Virus Research·Sirawat Srichatrapimuk, Prasert Auewarakul
Sep 15, 2009·Reviews in Medical Virology·David WarrilowDavid Harrich
Sep 30, 2015·Nature·Yoshiko UsamiHeinrich G Göttlinger
Sep 30, 2015·Nature·Annachiara RosaMassimo Pizzato
Oct 13, 2006·Virus Research·Tzanko S StantchevChristopher C Broder
Apr 22, 2015·Journal of Materials Science. Materials in Medicine·Mehdi Shafiee ArdestaniMohammad Reza Aghasadeghi
Apr 15, 2015·Assay and Drug Development Technologies·Mariana MarinGregory B Melikyan
May 5, 2009·Cell·Kosuke MiyauchiGregory B Melikyan
Jan 15, 2008·Virology·Mingli Qi, Christopher Aiken
May 11, 2006·Virology·Oliver T FacklerHans-Georg Kräusslich
Jun 7, 2014·Frontiers in Microbiology·Stéphane Basmaciogullari, Massimo Pizzato
Jun 28, 2016·Sensors·Daniel M Jones, Sergi Padilla-Parra
Sep 24, 2004·Virology·Marielle CavroisWarner C Greene
Mar 28, 2017·The Journal of Biological Chemistry·Tanay M DesaiGregory B Melikyan
Sep 10, 2005·Gene Therapy·E M Campbell, T J Hope
Feb 10, 2017·The Journal of Biological Chemistry·Chetan SoodGregory B Melikyan
Oct 21, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·David FenardWarner C Greene

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.