+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

A short isoform of human cytomegalovirus US3 functions as a dominant negative inhibitor of the full-length form

, : A short isoform of human cytomegalovirus US3 functions as a dominant negative inhibitor of the full-length form. Journal of Virology 80(11): 5397-5404

Human cytomegalovirus encodes four unique short (US) region proteins, each of which is independently sufficient for causing the down-regulation of major histocompatibility complex (MHC) class I molecules on the cell surface. This down-regulation enables infected cells to evade recognition by cytotoxic T lymphocytes (CTLs) but makes them vulnerable to lysis by natural killer (NK) cells, which lyse those cells that lack MHC class I molecules. The 22-kDa US3 glycoprotein is able to down-regulate the surface expression of MHC class I molecules by dual mechanisms: direct endoplasmic reticulum retention by physical association and/or tapasin inhibition. The alternative splicing of the US3 gene generates two additional products, including 17-kDa and 3.5-kDa truncated isoforms; however, the functional significance of these isoforms during viral infection is unknown. Here, we describe a novel mode of self-regulation of US3 function that uses the endogenously produced truncated isoform. The truncated isoform itself neither binds to MHC class I molecules nor prevents the full-length US3 from interacting with MHC class I molecules. Instead, the truncated isoform associates with tapasin and competes with full-length US3 for binding to tapasin; thus, it suppresses the action of US3 that causes the disruption of the function of tapasin. Our results indicate that the truncated isoform of the US3 locus acts as a dominant negative regulator of full-length US3 activity. These data reflect the manner in which the virus has developed temporal survival strategies during viral infection against immune surveillance involving both CTLs and NK cells.


PMID: 16699020

DOI: 10.1128/JVI.02397-05

Other references

Fleck, A.; Wunner, W.H.; Henderson, A.R.; Ballantyne, F.C.; Tilstone, W.J., 1971: Response of the liver to protein feeding. Proceedings of the Nutrition Society 30(1): 42-46

Vilhena, J.G.; Dumitru, A.C.; Herruzo, E.T.; Mendieta-Moreno, Jús.I.; Garcia, R.; Serena, P.A.; Pérez, Rén., 2016: Adsorption orientations and immunological recognition of antibodies on graphene. Large-scale molecular dynamics (MD) simulations and atomic force microscopy (AFM) in liquid are combined to characterize the adsorption of Immunoglobulin G (IgG) antibodies over a hydrophobic surface modeled with a three-layer graphene slab. We co...

Gallay, C., 1960: Physiological tests with nose drops. Pharmaceutica Acta Helvetiae 35: 358-374

Popov, Alexi, 1998: National action plan for conservation of biodiversity in Bulgaria. Historia Naturalis Bulgarica 9: 114

Metodieva, S.Nikolova.; Nikolova, D.Nikolaeva.; Cherneva, R.Vlaeva.; Dimova, I.Istalianova.; Petrov, D.Borisov.; Toncheva, D.Ivanova., 2011: Expression analysis of angiogenesis-related genes in Bulgarian patients with early-stage non-small cell lung cancer. Angiogenesis is a key process in the early stages of tumor development. In this study we aimed to evaluate the expression of a panel of angiogenesis-related genes in a group of Bulgarian patients with early-stage non-small cell lung cancer (NSCLC)...

Botjes, J.G.O., 1936: The status of the immunity problem in virus diseases of plante. The present position of the problem of immunity in relation to virus diseases of plants is discussed, with reference to current studies on the subject in Europe and the United States, under the following headings: selection of attenuated virus str...

Friederich, P.; Meded, V.; Symalla, F.; Elstner, M.; Wenzel, W., 2015: QM/QM approach to model energy disorder in amorphous organic semiconductors. It is an outstanding challenge to model the electronic properties of organic amorphous materials utilized in organic electronics. Computation of the charge carrier mobility is a challenging problem as it requires integration of morphological and e...

Nos D.Nicolau, M.Rosario, 1964: History and geography of the parrot. Zoo Rev Parque Zool Barcelona 3: 32-34

Urushibara, N.; Kumazaki, T.; Ishii, S., 1992: Hemoglobin-binding site on human haptoglobin. Identification of lysyl residues participating in the binding. The locus of human haptoglobin (Hp) molecules that interacts with human hemoglobin (Hb) was examined by the differential labeling technique. First, amino groups of Hp were extensively labeled with ethyl acetimidate (EAI) either in the free state (...

Thompson R.W.; Wadzinski M.G.; Sasse J.; Klagsbrun M.; Folkman J.; Shemin R.J.; D'amore P.A., 1986: Heparin binding endothelial cell growth factors from human myocardium. American Heart Association Monograph (124): II-288