Ablation of nectin4 binding compromises CD46 usage by a hybrid vesicular stomatitis virus/measles virus

Journal of Virology
Yu-Ping LiuKah-Whye Peng

Abstract

Measles virus (MV) immunosuppression is due to infection of SLAM-positive immune cells, whereas respiratory shedding and virus transmission are due to infection of nectin4-positive airway epithelial cells. The vaccine lineage MV strain Edmonston (MV-Edm) acquired an additional tropism for CD46 which is the basis of its oncolytic specificity. VSVFH is a vesicular stomatitis virus (VSV) encoding the MV-Edm F and H entry proteins in place of G. The virus spreads faster than MV-Edm and is highly fusogenic and a potent oncolytic. To determine whether ablating nectin4 tropism from VSVFH might prevent shedding, increasing its safety profile as an oncolytic, or might have any effect on CD46 binding, we generated VSVFH viruses with H mutations that disrupt attachment to SLAM and/or nectin4. Disruption of nectin4 binding reduced release of VSVFH from the basolateral side of differentiated airway epithelia composed of Calu-3 cells. However, because nectin4 and CD46 have substantially overlapping receptor binding surfaces on H, disruption of nectin4 binding compromised CD46 binding and greatly diminished the oncolytic potency of these viruses on human cancer cells. Thus, our results support continued preclinical development of VSVFH withou...Continue Reading

References

Jun 1, 1992·The Journal of Experimental Medicine·T J OglesbyJ P Atkinson
Sep 1, 1994·Trends in Microbiology·R E DörigC D Richardson
May 9, 1995·Proceedings of the National Academy of Sciences of the United States of America·N D LawsonJ K Rose
Sep 6, 2000·Nature·H TatsuoY Yanagi
May 2, 2002·Nature Medicine·Kah-Whye PengStephen J Russell
Jun 6, 2003·Current Opinion in Immunology·André Veillette, Sylvain Latour
Mar 3, 2004·Nature Biotechnology·Takafumi NakamuraStephen J Russell
Oct 21, 2005·Reviews in Medical Virology·Yann M KerdilesBranka Horvat
May 27, 2006·Experimental Hematology·Hooi Tin OngKah-Whye Peng
Dec 17, 2009·Nature Structural & Molecular Biology·César SantiagoJosé M Casasnovas
Nov 23, 2010·Expert Review of Vaccines·Patrycja J Lech, Stephen J Russell
Jan 11, 2011·Nature Structural & Molecular Biology·Takao HashiguchiYusuke Yanagi
Apr 5, 2011·Journal of Virological Methods·Jennifer L HarcourtLia M Haynes
Sep 9, 2011·PLoS Pathogens·Ryan S NoyceChristopher D Richardson
Nov 4, 2011·Nature·Michael D MühlebachRoberto Cattaneo
Dec 17, 2011·Human Gene Therapy·Camilo Ayala-BretonKah-Whye Peng
Jun 23, 2012·Trends in Microbiology·Ryan S Noyce, Christopher D Richardson
Sep 7, 2012·PLoS Pathogens·Rory D de VriesRik L de Swart
Dec 4, 2012·Nature Structural & Molecular Biology·Xiaoai ZhangGeorge F Gao
Jan 3, 2013·Reviews in Medical Virology·Melissa M CoughlinPaul A Rota
Jul 12, 2013·Molecular Therapy : the Journal of the American Society of Gene Therapy·Camilo Ayala-BretonKah-Whye Peng

❮ Previous
Next ❯

Citations

Jun 4, 2014·Viruses·Sebastien DelpeutChristopher D Richardson
Jan 29, 2017·Expert Opinion on Biological Therapy·Steven Robinson, Evanthia Galanis
Nov 17, 2017·The Journal of General Virology·Sébastien A Felt, Valery Z Grdzelishvili
Feb 22, 2018·PloS One·Miguel Ángel Muñoz-AlíaStephen J Russell

❮ 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.