Abstract
Feline leukemia virus (FeLV) C-Sarma (or FSC) is a prototype of subgroup C FeLVs, which induce fatal aplastic anemia in outbred specific-pathogen-free (SPF) cats. FeLV C isolates also possess an extended host range in vitro, including an ability, unique among FeLVs, to replicate in guinea pig cells. To identify the viral determinants responsible for the pathogenicity and host range of FSC we constructed a series of proviral DNAs by exchanging gene fragments between FSC and FeLV-61E (or F6A), the latter of which is minimally pathogenic and whose host range in vitro is restricted to feline cells. Transfer of an 886-base-pair (bp) fragment of FSC, encompassing the codons for 73 amino acids at the 3' end of pol (the integrase/endonuclease gene) and the codons for 241 amino acids of the N-terminal portion of env [the extracellular glycoprotein (gp70) gene], into the F6A genome was sufficient to confer onto chimeric viruses the ability to induce fatal aplastic anemia in SPF cats. In contrast, no chimera lacking this sequence induced disease. When assayed in vitro, all chimeric viruses containing the 886-bp fragment of FSC acquired the ability to replicate in heterologous cells, including dog and guinea pig cells. Thus, the pathogenic and the host range determinants of the feline aplastic anemia retrovirus colocalize to a 3' pol-5' env region of the FSC genome and likely reside within a region encoding 241 amino acid residues of the N terminus of the extracellular glycoprotein.
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- Appelbaum F. R., Fefer A. The pathogenesis of aplastic anemia. Semin Hematol. 1981 Oct;18(4):241–257. [PubMed] [Google Scholar]
- Celander D., Haseltine W. A. Tissue-specific transcription preference as a determinant of cell tropism and leukaemogenic potential of murine retroviruses. Nature. 1984 Nov 8;312(5990):159–162. doi: 10.1038/312159a0. [DOI] [PubMed] [Google Scholar]
- Chatis P. A., Holland C. A., Hartley J. W., Rowe W. P., Hopkins N. Role for the 3' end of the genome in determining disease specificity of Friend and Moloney murine leukemia viruses. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4408–4411. doi: 10.1073/pnas.80.14.4408. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chou P. Y., Fasman G. D. Prediction of protein conformation. Biochemistry. 1974 Jan 15;13(2):222–245. doi: 10.1021/bi00699a002. [DOI] [PubMed] [Google Scholar]
- Chung S. W., Wolff L., Ruscetti S. Sequences responsible for the altered erythropoietin responsiveness in spleen focus-forming virus strain SFFVP-infected cells are localized to a 678-base-pair region at the 3' end of the envelope gene. J Virol. 1987 May;61(5):1661–1664. doi: 10.1128/jvi.61.5.1661-1664.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DesGroseillers L., Rassart E., Jolicoeur P. Thymotropism of murine leukemia virus is conferred by its long terminal repeat. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4203–4207. doi: 10.1073/pnas.80.14.4203. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Donahue P. R., Hoover E. A., Beltz G. A., Riedel N., Hirsch V. M., Overbaugh J., Mullins J. I. Strong sequence conservation among horizontally transmissible, minimally pathogenic feline leukemia viruses. J Virol. 1988 Mar;62(3):722–731. doi: 10.1128/jvi.62.3.722-731.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Donehower L. A., Varmus H. E. A mutant murine leukemia virus with a single missense codon in pol is defective in a function affecting integration. Proc Natl Acad Sci U S A. 1984 Oct;81(20):6461–6465. doi: 10.1073/pnas.81.20.6461. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dorner A. J., Coffin J. M. Determinants for receptor interaction and cell killing on the avian retrovirus glycoprotein gp85. Cell. 1986 May 9;45(3):365–374. doi: 10.1016/0092-8674(86)90322-3. [DOI] [PubMed] [Google Scholar]
- Evans L. H., Morrey J. D. Tissue-specific replication of Friend and Moloney murine leukemia viruses in infected mice. J Virol. 1987 May;61(5):1350–1357. doi: 10.1128/jvi.61.5.1350-1357.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hagler L., Pastore R. A., Bergin J. J., Wrensch M. R. Aplastic anemia following viral hepatitis: report of two fatal cases and literature review. Medicine (Baltimore) 1975 Mar;54(2):139–164. [PubMed] [Google Scholar]
- Holland C. A., Hartley J. W., Rowe W. P., Hopkins N. At least four viral genes contribute to the leukemogenicity of murine retrovirus MCF 247 in AKR mice. J Virol. 1985 Jan;53(1):158–165. doi: 10.1128/jvi.53.1.158-165.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hoover E. A., Kociba G. J., Hardy W. D., Jr, Yohn D. S. Erythroid hypoplasia in cats inoculated with feline leukemia virus. J Natl Cancer Inst. 1974 Nov;53(5):1271–1276. doi: 10.1093/jnci/53.5.1271. [DOI] [PubMed] [Google Scholar]
- Jarrett O., Golder M. C., Toth S., Onions D. E., Stewart M. F. Interaction between feline leukaemia virus subgroups in the pathogenesis of erythroid hypoplasia. Int J Cancer. 1984 Aug 15;34(2):283–288. doi: 10.1002/ijc.2910340222. [DOI] [PubMed] [Google Scholar]
- Jarrett O., Laird H. M., Hay D. Determinants of the host range of feline leukaemia viruses. J Gen Virol. 1973 Aug;20(2):169–175. doi: 10.1099/0022-1317-20-2-169. [DOI] [PubMed] [Google Scholar]
- Kelleher J. F., Luban N. L., Mortimer P. P., Kamimura T. Human serum "parvovirus": a specific cause of aplastic crisis in children with hereditary spherocytosis. J Pediatr. 1983 May;102(5):720–722. doi: 10.1016/s0022-3476(83)80243-1. [DOI] [PubMed] [Google Scholar]
- Levin J. G., Hu S. C., Rein A., Messer L. I., Gerwin B. I. Murine leukemia virus mutant with a frameshift in the reverse transcriptase coding region: implications for pol gene structure. J Virol. 1984 Aug;51(2):470–478. doi: 10.1128/jvi.51.2.470-478.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Li Y., Golemis E., Hartley J. W., Hopkins N. Disease specificity of nondefective Friend and Moloney murine leukemia viruses is controlled by a small number of nucleotides. J Virol. 1987 Mar;61(3):693–700. doi: 10.1128/jvi.61.3.693-700.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Linemeyer D. L., Menke J. G., Ruscetti S. K., Evans L. H., Scolnick E. M. Envelope gene sequences which encode the gp52 protein of spleen focus-forming virus are required for the induction of erythroid cell proliferation. J Virol. 1982 Jul;43(1):223–233. doi: 10.1128/jvi.43.1.223-233.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mullins J. I., Brody D. S., Binari R. C., Jr, Cotter S. M. Viral transduction of c-myc gene in naturally occurring feline leukaemias. 1984 Apr 26-May 2Nature. 308(5962):856–858. doi: 10.1038/308856a0. [DOI] [PubMed] [Google Scholar]
- Nicolson M. O., Hariri F., Krempin H. M., McAllister R. M., Gilden R. V. Infectious proviral DNA in human cells infected with transformation-defective type C viruses. Virology. 1976 Apr;70(2):301–312. doi: 10.1016/0042-6822(76)90273-7. [DOI] [PubMed] [Google Scholar]
- Onions D., Jarrett O., Testa N., Frassoni F., Toth S. Selective effect of feline leukaemia virus on early erythroid precursors. Nature. 1982 Mar 11;296(5853):156–158. doi: 10.1038/296156a0. [DOI] [PubMed] [Google Scholar]
- Overbaugh J., Donahue P. R., Quackenbush S. L., Hoover E. A., Mullins J. I. Molecular cloning of a feline leukemia virus that induces fatal immunodeficiency disease in cats. Science. 1988 Feb 19;239(4842):906–910. doi: 10.1126/science.2893454. [DOI] [PubMed] [Google Scholar]
- Potter H., Weir L., Leder P. Enhancer-dependent expression of human kappa immunoglobulin genes introduced into mouse pre-B lymphocytes by electroporation. Proc Natl Acad Sci U S A. 1984 Nov;81(22):7161–7165. doi: 10.1073/pnas.81.22.7161. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Riedel N., Hoover E. A., Gasper P. W., Nicolson M. O., Mullins J. I. Molecular analysis and pathogenesis of the feline aplastic anemia retrovirus, feline leukemia virus C-Sarma. J Virol. 1986 Oct;60(1):242–250. doi: 10.1128/jvi.60.1.242-250.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Robinson H. L., Blais B. M., Tsichlis P. N., Coffin J. M. At least two regions of the viral genome determine the oncogenic potential of avian leukosis viruses. Proc Natl Acad Sci U S A. 1982 Feb;79(4):1225–1229. doi: 10.1073/pnas.79.4.1225. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Robinson H. L., Reinsch S. S., Shank P. R. Sequences near the 5' long terminal repeat of avian leukosis viruses determine the ability to induce osteopetrosis. J Virol. 1986 Jul;59(1):45–49. doi: 10.1128/jvi.59.1.45-49.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sarma P. S., Log T., Jain D., Hill P. R., Huebner R. J. Differential host range of viruses of feline leukemia-sarcoma complex. Virology. 1975 Apr;64(2):438–446. doi: 10.1016/0042-6822(75)90121-x. [DOI] [PubMed] [Google Scholar]
- Schwartzberg P., Colicelli J., Goff S. P. Construction and analysis of deletion mutations in the pol gene of Moloney murine leukemia virus: a new viral function required for productive infection. Cell. 1984 Jul;37(3):1043–1052. doi: 10.1016/0092-8674(84)90439-2. [DOI] [PubMed] [Google Scholar]
- Shadduck R. K., Winkelstein A., Zeigler Z., Lichter J., Goldstein M., Michaels M., Rabin B. Aplastic anemia following infectious mononucleosis: possible immune etiology. Exp Hematol. 1979 May;7(5):264–271. [PubMed] [Google Scholar]
- Silver B. J., Zuckerman K. S. Aplastic anemia: recent advances in pathogenesis and treatment. Med Clin North Am. 1980 Jul;64(4):607–629. doi: 10.1016/s0025-7125(16)31584-x. [DOI] [PubMed] [Google Scholar]
- Simon M. C., Neckameyer W. S., Hayward W. S., Smith R. E. Genetic determinants of neoplastic diseases induced by a subgroup F avian leukosis virus. J Virol. 1987 Apr;61(4):1203–1212. doi: 10.1128/jvi.61.4.1203-1212.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sitbon M., Sola B., Evans L., Nishio J., Hayes S. F., Nathanson K., Garon C. F., Chesebro B. Hemolytic anemia and erythroleukemia, two distinct pathogenic effects of Friend MuLV: mapping of the effects to different regions of the viral genome. Cell. 1986 Dec 26;47(6):851–859. doi: 10.1016/0092-8674(86)90800-7. [DOI] [PubMed] [Google Scholar]
- Wolff L., Ruscetti S. Tissue tropism of a leukemogenic murine retrovirus is determined by sequences outside of the long terminal repeats. Proc Natl Acad Sci U S A. 1986 May;83(10):3376–3380. doi: 10.1073/pnas.83.10.3376. [DOI] [PMC free article] [PubMed] [Google Scholar]