RESUMO
Murine γ-herpesvirus 68 (MHV-68) infection of Mus musculus-derived strains of mice is an established model of γ-herpesvirus infection. We have previously developed an alternative system using a natural host, the wood mouse (Apodemus sylvaticus), and shown that the MHV-68 M3 chemokine-binding protein contributes significantly to MHV-68 pathogenesis. Here we demonstrate in A. sylvaticus using high-density micro-arrays that M3 influences the expression of genes involved in the host response including Scgb1a1 and Bpifa1 that encode potential innate defense proteins secreted into the respiratory tract. Further analysis of MHV-68-infected animals showed that the levels of both protein and RNA for SCGB1A1 and BPIFA1 were decreased at day 7 post infection (p.i.) but increased at day 14 p.i. as compared with M3-deficient and mock-infected animals. The modulation of expression was most pronounced in bronchioles but was also present in the bronchi and trachea. Double staining using RNA in situ hybridization and immunohistology demonstrated that much of the BPIFA1 expression occurs in club cells along with SCGB1A1 and that BPIFA1 is stored within granules in these cells. The increase in SCGB1A1 and BPIFA1 expression at day 14 p.i. was associated with the differentiation of club cells into mucus-secreting cells. Our data highlight the role of club cells and the potential of SCGB1A1 and BPIFA1 as innate defense mediators during respiratory virus infection.
Assuntos
Gammaherpesvirinae/genética , Glicoproteínas/metabolismo , Infecções por Herpesviridae/metabolismo , Infecções por Herpesviridae/virologia , Fosfoproteínas/metabolismo , Uteroglobina/metabolismo , Animais , Bronquíolos/química , Bronquíolos/citologia , Bronquíolos/metabolismo , Bronquíolos/virologia , Glicoproteínas/genética , Infecções por Herpesviridae/genética , Interações Hospedeiro-Patógeno/genética , Murinae , Fosfoproteínas/genética , Mucosa Respiratória/química , Mucosa Respiratória/citologia , Mucosa Respiratória/metabolismo , Mucosa Respiratória/virologia , Uteroglobina/genéticaRESUMO
Murine γ-herpesvirus 68 (MHV-68) infection of Mus musculus-derived strains of mice is an attractive model of γ-herpesvirus infection. Surprisingly, however, ablation of expression of MHV-68 M3, a secreted protein with broad chemokine-binding properties in vitro, has no discernable effect during experimental infection via the respiratory tract. Here we demonstrate that M3 indeed contributes significantly to MHV-68 infection, but only in the context of a natural host, the wood mouse (Apodemus sylvaticus). Specifically, M3 was essential for two features unique to the wood mouse: virus-dependent inducible bronchus-associated lymphoid tissue (iBALT) in the lung and highly organized secondary follicles in the spleen, both predominant sites of latency in these organs. Consequently, lack of M3 resulted in substantially reduced latency in the spleen and lung. In the absence of M3, splenic germinal centers appeared as previously described for MHV-68-infected laboratory strains of mice, further evidence that M3 is not fully functional in the established model host. Finally, analyses of M3's influence on chemokine and cytokine levels within the lungs of infected wood mice were consistent with the known chemokine-binding profile of M3, and revealed additional influences that provide further insight into its role in MHV-68 biology.
Assuntos
Quimiocinas/imunologia , Gammaherpesvirinae/fisiologia , Infecções por Herpesviridae/imunologia , Proteínas Virais/imunologia , Animais , Brônquios/imunologia , Brônquios/virologia , Linhagem Celular , Quimiocinas/genética , Cricetinae , Infecções por Herpesviridae/genética , Pulmão/imunologia , Pulmão/virologia , Tecido Linfoide/imunologia , Tecido Linfoide/virologia , Camundongos , Murinae , Baço/imunologia , Baço/virologia , Proteínas Virais/genética , Latência Viral/genética , Latência Viral/imunologiaRESUMO
Soft tissue sarcomas of the equine distal limb associated with joints, sheaths, or bursae have rarely been reported. Accurate diagnosis of these tumors is challenging in both human beings and veterinary species. Immunohistochemical staining and transmission electron microscopy have been used in human beings to reduce misdiagnosis. The current report describes 2 mature horses presenting with lameness and swelling associated with the dorsal aspect of the metacarpo(tarso)phalangeal joint. In both cases, surgical excision was performed with subsequent histological analysis of the masses to determine the tissue of origin. In both cases, immunohistochemical staining and transmission electron microscopy aided the definitive diagnosis of fibrosarcoma associated with the fetlock joints of 2 horses.