The erythrocyte viral trap: transgenic expression of viral receptor on erythrocytes attenuates coxsackievirus B infection.
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.
Asher
Damon R
DR
Department of Medicine, University of Massachusetts Medical School, 227 Lazare Research Building, 364 Plantation Street, Worcester, MA 01605, USA.
Cerny
Anna M
AM
Finberg
Robert W
RW
D000818:Animals; D003384:Coxsackievirus Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004770:Enterovirus / Q000502:physiology*; D004912:Erythrocytes / Q000378:metabolism* / Q000821:virology*; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D015996:Survival Rate; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D019076:Transgenes / Q000235:genetics; D014766:Viremia / Q000378:metabolism / Q000821:virology
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; C494689:Gata1 protein, mouse; D011991:Receptors, Virus; D014157:Transcription Factors; C085301:adenovirus receptor