The erythrocyte viral trap: transgenic expression of viral receptor on erythrocytes attenuates coxsackievirus B infection
Department of Medicine, Division of Infectious Diseases and Immunology
Animals; Coxsackievirus Infections; DNA-Binding Proteins; Enterovirus; Erythrocytes; Erythroid-Specific DNA-Binding Factors; GATA1 Transcription Factor; Gene Expression; Humans; Mice; Mice, Transgenic; Receptors, Virus; Survival Rate; Transcription Factors; Transgenes; Viremia
Life Sciences | Medicine and Health Sciences
Viruses rely on attachment to specific cell surface receptors to infect host cells. Selective expression of viral receptors has the potential to attenuate infection of susceptible tissues by redirecting virus to cells that cannot support viral replication. We propose that erythrocytes are an ideal instrument for this strategy, because they are present in vast numbers, permeate every organ, and cannot serve as hosts for viral propagation. To test this hypothesis, we generated a transgenic mouse, termed globin transcription factor 1 (GATA1)-coxsackie and adenovirus receptor (CAR), that expressed the CAR on erythrocytes. Coxsackievirus group B (CVB) adhered to the surface of CAR-expressing erythrocytes and was rendered noninfectious. Upon infection with CVB, GATA1-CAR mice had diminished viremia and reduced viral replication in heart, brain, and liver. Furthermore, when faced with a CVB challenge that was lethal to WT littermates, the survival of GATA1-CAR mice was prolonged, and their ultimate mortality was reduced. The GATA1-CAR mouse model presented here demonstrates that erythrocyte expression of CAR limits CVB pathogenesis. Erythrocytes also may be coated with a variety of receptors by nontransgenic methods, making this a very flexible model for the treatment of infectious diseases in humans.
DOI of Published Version
Proc Natl Acad Sci U S A. 2005 Sep 6;102(36):12897-902. Epub 2005 Aug 25. Link to article on publisher's site
Proceedings of the National Academy of Sciences of the United States of America
Asher, Damon R.; Cerny, Anna M.; and Finberg, Robert W., "The erythrocyte viral trap: transgenic expression of viral receptor on erythrocytes attenuates coxsackievirus B infection" (2005). Open Access Articles. 1755.