Field isolates of foot-and-mouth disease virus (FMDV) have been shown to use the RGD-dependent integrin ␣v3 as a cellular receptor on cultured cells. However, several other RGD-dependent integrins may have the potential to act as receptors for FMDV in vivo. Of these, ␣v6 is a likely candidate for use as a receptor by FMDV as it is expressed on epithelial cells, which correlates with the tissue tropism of the virus. In this report, we show that human colon carcinoma cells (SW480) that are normally nonpermissive for FMDV become susceptible to infection as a result of transfection with the integrin 6 subunit and expression of ␣v6 at the cell surface. Integrin ␣v6 is the major site for virus attachment on the 6-transfected cells, and binding to ␣v6 serves to increase the rate of virus entry into these cells. In addition, we show that virus binding and infection of the 6-transfected cells is mediated through an RGD-dependent interaction that is specifically inhibited by a monoclonal antibody (10D5) that recognizes ␣v6. These studies establish a role for ␣v6 as a cellular receptor for FMDV.
To understand the mechanisms involved in protective immunity to African swine fever virus (ASFV) infection, the observation that infection with the avirulent Portuguese ASFV isolate OUR/T88/3 protects outbred pigs from challenge with the virulent Portuguese ASFV isolate OUR/T88/1 was exploited. It was demonstrated that pigs exposed to OUR/T88/3 and then depleted of CD8 + lymphocytes were no longer fully protected from OUR/T88/1 challenge. This indicated that CD8 + lymphocytes play an important role in the protective immune response to ASFV infection and that anti-ASFV antibody alone, from OUR/T88/3 infection, was not sufficient to protect pigs from OUR/T88/1 challenge. Inbred pigs of the cc haplotype infected with OUR/T88/3 were not always protected from OUR/T88/1 challenge and developed both viraemia and fever. Such viraemia was always correlated with increased numbers of circulating CD8b + lymphocytes, indicating a specific role for CD8b + lymphocytes in combating viraemia. These experiments indicate an important role for CD8 + lymphocytes, particularly CD8b + lymphocytes, in ASF protective immunity.
Title: Viral targeting of non-muscle invasive bladder cancer and priming of anti-tumour immunity following intravesical Coxsackievirus A21 Running Title: Viral targeting of non-muscle invasive bladder cancer.
As a clinical setting in which local live biological therapy is already well established, non-muscle invasive bladder cancer (NMIBC) presents intriguing opportunities for oncolytic virotherapy. Coxsackievirus A21 (CVA21) is a novel intercellular adhesion molecule-1 (ICAM-1)-targeted immunotherapeutic virus. This study investigated CVA21-induced cytotoxicity in a panel of human bladder cancer cell lines, revealing a range of sensitivities largely correlating with expression of the viral receptor ICAM-1. CVA21 in combination with low doses of mitomycin-C enhanced CVA21 viral replication and oncolysis by increasing surface expression levels of ICAM-1. This was further confirmed using 300-μm precision slices of NMIBC where levels of virus protein expression and induction of apoptosis were enhanced with prior exposure to mitomycin-C. Given the importance of the immunogenicity of dying cancer cells for triggering tumor-specific responses and long-term therapeutic success, the ability of CVA21 to induce immunogenic cell death was investigated. CVA21 induced immunogenic apoptosis in bladder cancer cell lines, as evidenced by expression of the immunogenic cell death (ICD) determinant calreticulin, and HMGB-1 release and the ability to reject MB49 tumors in syngeneic mice after vaccination with MB49 cells undergoing CVA21 induced ICD. Such CVA21 immunotherapy could offer a potentially less toxic, more effective option for the treatment of bladder cancer.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.