A replication-defective variant of feline leukemia virus was molecularly cloned directly from infected tissue and found to induce a rapid and fatal immunodeficiency syndrome in cats. Studies with cloned viruses also showed that subtle mutational changes would convert a minimally pathogenic virus into one that would induce an acute form of immunodeficiency. The data suggest that acutely pathogenic viruses may be selected against by current methods for isolation of the human and simian immunodeficiency viruses.

SEN virus (SEN-VAfter cloning of the hepatitis C virus (HCV) 1 and development of sensitive serologic and molecular assays for this pathogen, a dramatic decline in the incidence of transfusionassociated hepatitis occurred. 2,3 However, approximately 10% of transfusion-associated hepatitis cases 4 and 20% of community-acquired hepatitis cases 5 do not have a defined etiology suggesting the existence of additional causative agents. Hepatitis G virus (HGV), 6 also known as GB virus C (GBV-C), 7 was initially suggested as a causative agent of non-A to E hepatitis, but this was not confirmed in further studies. [8][9][10] The originally described TT virus (TTV), discovered in 1997 by representational difference analysis, was detected in 3 of 5 cases of transfusion-associated hepatitis and was proposed as a potential cause of non-A to E hepatitis. 11 Using TTV primers identical to those reported, non-A to E hepatitis cases and controls in the NIH prospective series were tested but no association with transfusion-associated hepatitis was found. 12 Subsequently, primers to more conserved regions of the TTV genome were used in studies in Japan, and the agent was found in greater than 90% of Japanese blood donors. 13 This further diminished the likelihood that TTV was the cause of transfusion-associated hepatitis and precluded the possibility of a practical screening assay. Other studies have also confirmed the high prevalence of TTV and its lack of association with transfusion-associated hepatitis. 14,15 Recently, a novel DNA virus designated SEN virus (SEN-V) was discovered in the serum of an intravenous drug abuser also infected with human immunodeficiency virus. 16,17 SEN-V was initially described as a single-stranded DNA virus of approximately 3,800 nucleotides. 16 Phylogenetic analysis of SEN-V has shown the existence of 8 strains. 18 Although structurally similar to TTV, SEN-V has less than 55% sequence homology and less than 37% amino acid homology with the TTV prototype. 18 Preliminary studies of SEN-V variants were conducted by Dr. Primi (DiaSorin Inc., Brescia, Italy). The prevalence of 5 SEN-V strains (A, B, H [former C], D, and E) and a consensus sequence designated total SEN-V were measured in various donor and patient populations. It was shown that measuring total SEN-V was not practical because the prevalence in donors was 13% and the rate in all transfused populations exceeded 70%. SENV-B was also excluded as a useful screening assay because it was present in 10% of donors and only 8% of patients with transfusion-associated non-A to E hepatitis. SENV-A and SENV-E were found in low prevalence in donors, but did not appear to be associated with non-A to E hepatitis. In contrast, SENV-D and SENV-H had favorable prevalence ratios being found in less than 1% of donors and more than 50% of transfusion-associated non-A to E cases. These initial polymerase chain reaction (PCR) data were confirmed by cloning and sequencing which showed that SENV-D and SENV-H sequences were found in a high proportion of non-A to E ...

We report the first complete nucleotide sequence (8,440 base pairs) of a biologically active feline leukemia virus (FeLV), designated FeLV-61E (or F6A), and the molecular cloning, biological activity, and env-long terminal repeat (LTR) sequence of another FeLV isolate, FeLV-3281 (or F3A). F6A corresponds to the non-disease-specific common-form component of the immunodeficiency disease-inducing strain of FeLV, FeLV-FAIDS, and was isolated from tissue DNA of a cat following experimental transmission of naturally occurring feline acquired immunodeficiency syndrome. F3A clones were derived from a subgroup-A-virusproducing feline tumor cell line. Both are unusual relative to other molecularly cloned FeLVs studied to date in their ability to induce viremia in weanling (8-week-old) cats and in their failure to induce acute disease. The F6A provirus is organized into 5'-LTR-gag-pol-env-LTR-3' regions; the gag and pol open reading frames are separated by an amber codon, and env is in a different reading frame. The deduced extracellular glycoproteins of F6A, F3A, and the Glasgow-l subgroup A isolate of FeLV (M.

Within the fatal immunodeficiency disease-inducing strain of feline leukemia virus, FeLV-FAIDS, are viruses which range in pathogenicity from minimally (clone 61E is the prototype) to acutely pathogenic, most of the latter of which are also replication defective (clone 61C is the prototype). Mixtures of 61E and 61C virus and chimeras generated between them, but not 61E alone, killed feline T cells. T-cell killing depended on changes within a 7-amino-acid region near the C terminus of the gp7O env gene or was achieved independently by changes within a 109-amino-acid region encompassing the N terminus of gp7O. The carboxy-terminal change was also sufficient for induction of fatal immunodeficiency disease in cats. Other changes within the 61C gp7O gene enhanced T-cell killing, as did changes in the long terminal repeat, the latter of which also enhanced virus replication. T-cell killing correlated with high levels of intracellular unintegrated and proviral DNA, all of which were blocked by treatment of infected cells with sera from 61C-immune cats or with a neutralizing monoclonal antibody. These findings indicate that T-cell killing is a consequence of superinfection and that the mutations in env critical to pathogenicity of the immunosuppressive variant result in a failure to establish superinfection interference in infected cells. * Corresponding author. a feline T-cell line as an in vitro correlate of disease induction, and delimit aspects of the mechanism of T-cell killing.