Disease-specific and tissue-specific production of unintegrated feline leukaemia virus variant DNA in feline AIDS

Feline leukaemia viruses (FeLVs) have long been known to be associated with induction of proliferative and anti-proliferative diseases of domestic cats. Strains of FeLV have been recognized which specifically induce lymphosarcoma, aplastic anaemia, myelodysplastic anaemia, and, recently, feline AIDS (acquired immune deficiency syndrome), a naturally occurring immunosuppressive syndrome strikingly similar to human AIDS which is lethal in 100% of inoculated and viraemic specific-pathogen-free (SPF) cats. Here, we have analysed FeLV DNA in tissues of 22 SPF cats that had been inoculated with the feline AIDS strain (FeLV-FAIDS) and we find two classes of viral DNA--a monotypic common form which is detectable in bone marrow regardless of disease state, and variant forms, recognizable by restriction site differences, whose appearance correlates with onset of disease symptoms and persists throughout the course of the disease. FeLV-FAIDS variant DNA is detected at high concentration (10-50 copies per cell) and principally as unintegrated viral DNA (UVD) in bone marrow of cats with feline AIDS. In marked contrast high levels of UVD were not present in cats in the terminal-stages of T-cell lymphosarcoma, aplastic anaemia, or myelodysplastic anaemia induced by other FeLV strains. These results parallel recent observations in humans, where high levels of UVD were sometimes found in cells derived from AIDS patients infected with human T-lymphotropic virus type III (HTLV-III)/lymph-adenopathy-associated virus (LAV), and suggest that persistence of unintegrated variant viral DNA is a crucial indicator of retrovirus-induced cytopathic disease syndromes such as AIDS.     

Transduction of endogenous envelope genes by feline leukaemia virus in vitro

Feline leukaemia viruses (FeLV) are exogenous retroviruses that can be detected in most cats with leukaemia, aplastic anaemia, myeloproliferative diseases and fatal immunosuppression. FeLV isolates have been divided into three subgroups, based on the viral envelope-determined properties of interference and host range in vitro. FeLV-A is present in all natural isolates and is generally minimally pathogenic. FeLV-B is found with FeLV-A in isolates from approximately 40% of natural infections and in a higher percentage of cats with lymphoma. Following the fundamental observations of genetic reassortment of avian retroviruses with endogenous viral genes and the origination of lymphomagenic viruses during the ontogeny of AKR mice, we show here that transfection of feline cells with FeLV-A DNA results in its recombination with endogenous FeLV-related sequences to produce viruses with the structural and host range properties of FeLV-B. Thus in vitro propagation of a retrovirus may result in the generation of variants with very different properties.     

Transduction and rearrangement of the myc gene by feline leukaemia virus in naturally occurring T-cell leukaemias

Evidence of myc gene transduction by feline leukaemia virus in several spontaneous lymphoid tumours of cats suggests that recombinant viruses carrying oncogenes may be much more involved in oncogenesis in natural conditions than previously recognized.     

Isolation of a feline leukaemia provirus containing the oncogene myc from a feline lymphosarcoma

The molecular mechanism by which feline leukaemia virus (FeLV) induces lymphoid malignancy in domestic cats is largely unknown. Using the insertional activation model of c-myc by avian leukosis virus in the induction of bursal lymphoma in chickens, we have now characterized the c-myc locus in feline tissues and investigated the possibility that FeLV may also insert within feline c-myc. We used the 1.5 kilobase (kb) PstI fragment of MC29 v-myc in Southern blot analysis to characterize the structure of the c-myc locus in the DNA of 31 naturally occurring feline lymphomas. Analysis of a cloned c-myc gene from one lymphoma demonstrated that sequences homologous to v-myc occupy 2.6 kb of feline DNA in which a putative intron of 0.5 kb separates sequences homologous to the 5' and 3' exons represented in avian v-myc. We also observed in the DNA of this lymphoma tumour-specific fragments homologous to v-myc. Characterization of these molecularly cloned myc-hybridizing fragments revealed the presence of at least two identical FeLV proviruses 5.5 kb in length, each containing long terminal repeats enclosing a spliced version of the feline myc gene.     

onc sequences (v-fes) of Snyder-Theilen feline sarcoma virus are derived from noncontiguous regions of a cat cellular gene (c-fes)

Type C sarcoma viruses are genetic recombinants containing portions of replication-competent helper viruses linked to sarcoma virus-specific sequences (generically designated onc genes) which are thought to be required for acute fibroblast transformation. The onc elements of different avian and mammalian sarcoma viral isolates are each homologous to subsets of cellular DNA sequences which have no well-defined role in normal cells. Because of the lack of significant homology between helper viral genes and cellular onc sequences, the recombinational mechanisms which facilitate the formation of sarcoma viral genomes remain unclear. In Moloney murine sarcoma virus, viral onc (or v-mos) and cellular onc (or c-mos) sequences exhibit complete and uninterrupted homology as determined by heteroduplex and restriction enzyme analyses of molecularly cloned DNA. By contrast, the cellular counterparts of the onc elements of Rous sarcoma virus (G. Cooper and R. Parker, personal communication), avian erythroblastosis virus (B. Vennstrom, personal communication), Abelson leukaemia virus (D. Baltimore, personal communication), Harvey sarcoma virus (E. Scolnick, personal communication) and simian sarcoma virus (R. Gallo, personal communication) are now known to contain intervening sequences which do not appear in the respective viral genomes. Here we report the use of the Southern blot technique to examine cat cellular DNA sequences (c-fes) homologous to the onc gene (v-fes) of Snyder-Theilen feline sarcoma virus (ST-FeSV). We used cloned DNA 'probes' containing defined portions of the ST-FeSV genome to show that v-fes sequences originate from at least four noncontiguous sequences in cat cellular DNA, separated from each other by intervening sequences.     

犬猫乳腺癌的病理学观察

7例犬猫乳腺肿瘤被分别诊断为乳腺硬化性腺癌、髓样癌、乳头状腺癌、管状腺癌,并对犬猫乳腺肿瘤、乳腺癌的发生、预防、形态及诊断进行了讨论.