Compared with intraperitoneal injection, intravascular inoculation of SV40 strains resulted in more neutralizing antibody responses and higher titers of antibody. regulatory regions induced TAg antibody more often than did viruses with simple regulatory regions after intraperitoneal but not intravascular injections, with no differences in antibody titers. This viral genetic variation experienced no effect on neutralizing antibody production after intraperitoneal or intravascular inoculations or on neutralizing antibody titers achieved. These findings confirm that SV40 variants differ in their biologic properties. Route of inoculation combined with viral genetic variation significantly influence the development of serum antibodies to SV40 TAg in tumor-free hamsters. Route of inoculationbut not viral genetic variationis an important factor in production of neutralizing antibody to SV40. value of 0.05 or less was considered statistically significant. All statistical analyses were performed by using SAS software (version 9.2, SAS Institute, Cary, NC). Results Characterization of antibody responses to SV40 viral Grazoprevir proteins in hamsters. The majority of SV40 tumor-bearing hamsters have antibodies against SV40 TAg (the viral oncoprotein). In addition, many virus-exposed hamsters respond immunologically to TAg yet do not develop tumors.27,35,40 Factors affecting the T-antibody responses in the absence of tumors have not been analyzed. The current study examined T-antibody responses in archival sera from SV40-inoculated hamsters that experienced remained tumor-free for 9 to 12 mo after inoculation. We compared 3 routes of inoculation, 2 of which involved injection into the bloodstream (intracardiac, intravenous); the other was injection into the intraperitoneal cavity (Table 1). In addition, we assessed multiple SV40 strains, including those with either simple (1E) or complex (2E) regulatory regions, to examine viral genetic influences on serologic responses. A total of 167 virus-exposed, tumor-free hamsters were analyzed, as well as 43 control animals that had been inoculated with uninfected cell lysate. Table 1 shows the percentage of hamsters positive for TAg antibodies and for viral neutralizing antibodies in each experimental group. Table 1. SV40 T-antigen IgG and neutralizing antibody in sera from tumor-free hamsters at 9 to 12 mo after computer Grazoprevir virus inoculation 0.05) more antibody-positive responses occurred when hamsters were inoculated by the intravascular route as compared with the intraperitoneal route. This observation was consistent whether all the viruses were considered together (intravascular, 89%; intraperitoneal, 59%; = 0.001) or whether computer virus variants with complex (2E) or simple (1E) regulatory regions were compared separately with intraperitoneal injections (90% compared with 68%, = 0.02; 88% compared with 45%, = 0.003, respectively). Whereas the frequency of generation of antibody to TAg differed between 2E and 1E viruses that were launched intraperitoneally (68% compared with 45%, = 0.01), no such difference was apparent after intravascular injection (90% compared with 81%, = 0.2). There were no differences in T-antibody responses when the intracardiac and intravenous routes were compared (= 0.2) or when the 2 2 independent experiments involving intraperitoneal injections were compared for all those viruses (= 0.4), for 1E viruses only (= 0.7), or for 2E variants only (= 0.8). We also compared neutralizing antibody responses, which are directed against the SV40 viral capsid (Table 2). Presumably, this immune response was elicited primarily by the inoculated computer virus particles and was not dependent on computer virus replication. The superiority of the intravascular route over the intraperitoneal route of inoculation on SV40 neutralizing antibody production was even more pronounced than that for TAg IgG antibody, with more significant effects for all those computer virus variants compared together Rabbit Polyclonal to MAD4 (100% compared with 51%, 0.0001), for 2E viruses only (100% compared with 50%, 0.0001), and for 1E viruses only (100% compared with 53%, = 0.001). However, in contrast to TAg antibody, frequency of neutralizing antibody responsiveness between the 2E and 1E viruses was not different after intraperitoneal (50% Grazoprevir compared with 53%, = 0.73) or intravascular (100% compared with 100%, = 1.0) inoculation. This result is not unexpected, given that the viral capsid is the same for all the computer virus variants. Significant differences in frequency of neutralizing antibody production were not detected in individual experiments including intracardiac and intravenous injections (= 1.0) or in the 2 2 intraperitoneal experiments that compared viruses with simple regulatory regions (= 0.2). However, a difference in neutralizing antibody responses was detected between the 2 IP experiments that compared 2E viruses (= 0.03; the IP-A experiment included only a single 2E computer virus). We then assessed whether route of inoculation or viral factors significantly influenced the titers of antibody-positive responses;.