Influence of MHC on the oncogenicity and immunogenicity of polyoma virus BK in rats.

The oncogenicity of the human papovavirus, type BK, was examined in the Lewis strain of inbred rats, possessing the recombinant alleles "a" and "u" on the MHC TR1 locus. It was found that only haplotypes containing "a" within the B/D locus but not within the A and the C locus of the RT1 region were associated with resistance to the oncogenic potential of BKV and with the capacity of animals to form BKV T antigen antibody. By contrast, the presence of "u" or "l" within the MHC B/D region was linked to the reverse phenotype characterized by sensitivity to the oncogenic effect of BKV and failure to yield T antibody response up to 6 months after inoculation with BK. These results present further evidence of the function as an immune control gene of the B/D region of the RT1 locus of rat MHC.

Human polyoma virus type BK infection and T antibody response in renal transplant recipients.

BKV infections were detected in 103 of 168 renal transplant recipients. 18 patients showed primary infection within 3 months after transplantation as evidenced by seroconversion and virus isolation. Secondary BKV infection occurred in 44 patients generally more than 3 months after transplantation and was recorded in terms of significant BKV antibody titer increases. Patients with BKV infection had detectable BKV IgM over an observation period of 3 to 8 years, indicating persistence of BKV infection. T antibody was detected in 30 of 103 BKV infected patients. These antibodies were found more frequently in patients with primary than in those with secondary infection and persisted for many years. No T antibody was detected in patients without BKV infection. The presence of T antibodies was significantly associated with the HLA determinants A 30 and DRw 6.

Oncogenic activity of the BK type of human papova virus in inbred rat strains.

The oncogenicity of the human polyomavirus BK (BKV) was tested in newborn inbred rats. It was found that the tumor rate was negatively correlated with the levels of T antibody 3 months after inoculation and the frequency of animals with detectable T antibodies 1.5 months after inoculation. By contrast, no influence of viral HI titers on the tumor rates was found. Thymectomy of animals resulted in most experiments in increased tumor rates. Inoculation with BKV of animals later than 24 hours after birth yielded a decrease of tumor rates. The results obtained suggest that T antibody titers present at a critical time after inoculation are associated with low oncogenicity of BKV. The oncogenicity of BKV was comparatively tested in rat strains possessing the allele "l" or the allele "a", respectively. The oncogenicity was significantly higher in rats with the allele "l" than in rats with the allele "a". Rats with the allele "l" showed lower T antibody response than rats with the allele "a". These differences could be explained by the finding that cells of "a" origin showed in vitro a higher percentage of T antigen bearing cells than did cells of a strain possessing the allele "l". In comparison to previous results obtained with BKV inoculated outbred WISTAR rats, the oncogenicity of comparable BKV doses in inbred rats was generally higher and the latency period of tumor manifestation shortened.

Association of minimal change nephrotic syndrome (MCNS) with HLA-B8 an B13.

HLA antigens of 45 children with idiopathic nephrotic syndrome were typed for 26 phenotypic specificities. A significant association of MCNS with HLA-B 8 and B 13 was found. There was also a significantly increased frequency of the antigen combination HLA-A 1/B 8 (most presumably the haplo-type). The association with HLA-B 8 provides further evidence of an important role of immune mechanisms in the pathogenesis of MCNS.

Oncogenic activity of the BK type of human papova virus in newborn Wistar rats.

The oncogenic potential of the human papova virus BK (= BKV) has been examined in newborn Wistar rats. 12 of 37 animals inoculated with BKV s.c. and 7 of 40 animals inoculated with BKV i.c. developed tumors of various histological types. The latency periods ranged from 6 to 18 months. The BKV etiology of tumors was supported by detection of BKV T antigen in cells of established tumor lines by means of indirect immunofluorescence. No tumors appeared in animals given injections of saline instead of virus. BKV T antibodies were detected in sera of 100 per cent of animals bearing tumors but no in sera of control animals. Only 3 of 77 BKV infected and none of the control animals developed spontaneous tumors (adenomas).

Antioncogenic activity of influenza virus on polyoma virus induced renal and brain tumors in newborn Wistar rats.

Simultaneous inoculation of newborn Wistar rats with intact A/PR 8/34 (HON 1) influenza virus and the S.E. strain of polyoma virus resulted in significant reduction of the rates of both kidney sarcomas and brain tumors in comparison to controls given polyoma virus, only. This antioncogenic activity (AOA) of influenza virus was observed independently whether or not influenza and polyoma virus were injected on different sites or were inoculated as a combined vaccine. Ether-treated A/PR 8/34 influenza virus was found to have also AOA. However, in one experiment a significant AOA was demonstrated with respect to brain tumors, only, and not for the rate of renal sarcomas. In addition, the influenza strain A/Hong Kong/1/68 (H3N2) was found to have AOA.