The chemokine IL8 is up-regulated in bovine endometrial stromal cells by the BoHV-4 IE2 gene product, ORF50/Rta: a step ahead toward a mechanism for BoHV-4 induced endometritis.
Postpartum infections of the endometrium and metritis are common causes of delayed conception and infertility in cattle. These infections are characterized by inflammation of the endometrium and secretion of the chemokine interleukin 8 (IL8), which attracts granulocytes to the endometrium. Bovine herpesvirus 4 (BoHV-4) is tropic for the endometrium and the only virus consistently associated with postpartum metritis. The BoHV-4 Immediate Early 2 (IE2) gene is the first viral gene transcribed by host cells after infection, and the IE2 gene product, ORF50/Rta, transactivates host cell genes. The present study tested the hypothesis that ORF50/Rta transactivates the IL8 gene promoter during BoHV-4 infection of bovine endometrial stromal cells (BESCs). Infection of primary BESCs with BoHV-4 stimulated IL8 gene promoter activity and IL8 protein secretion. However, IL8 production was dependent on the transcription of viral genes, because psoralen/ultraviolet cross-linking of the viral DNA abrogated the response to BoHV-4 infection. Furthermore, IL8 promoter serial deletion analysis revealed a specific region responsive to ORF50/Rta. These observations may represent an endometrial defense mechanism against viral infection or a virulence mechanism by which viral replication stimulates chemokine secretion to attract more susceptible host cells to the endometrium.
Donofrio
Gaetano
G
Sezione di Malattie Infettive degli Animali, Dipartimento di Salute Animale, Facoltà di Medicina Veterinaria, Università di Parma, Parma, Italy. gaetano.donofrio@unipr.it
Capocefalo
Antonio
A
Franceschi
Valentina
V
Price
Sian
S
Cavirani
Sandro
S
Sheldon
Iain Martin
IM
D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002418:Cattle Diseases / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D002460:Cell Line; D002478:Cells, Cultured; D004716:Endometritis / Q000378:metabolism / Q000662:veterinary / Q000821:virology*; D004717:Endometrium / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006566:Herpesviridae Infections / Q000276:immunology / Q000662:veterinary* / Q000821:virology; D026021:Herpesvirus 4, Bovine / Q000187:drug effects / Q000378:metabolism; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014412:Tumor Virus Infections / Q000276:immunology / Q000662:veterinary* / Q000821:virology; D015854:Up-Regulation; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D038301:Virus Inactivation / Q000187:drug effects
C079185:IE2 protein, bovine herpesvirus type 4; D017874:Immediate-Early Proteins; D016209:Interleukin-8; D012333:RNA, Messenger; D015534:Trans-Activators; D014764:Viral Proteins