Abstract
We constructed recombinant feline herpesviruses (FHVs) expressing the envelope (env) and gag genes of feline leukemia virus (FeLV). Expression cassettes, utilizing the human cytomegalovirus immediate-early promoter, were inserted within the thymidine kinase gene of FHV. The FeLV env glycoprotein expressed by recombinant FHV was processed and transported to the cell surface much as in FeLV infection, with the exception that proteolytic processing to yield the mature gp70 and p15E proteins was less efficient in the context of herpesvirus infection. Glycosylation of the env protein was not affected; modification continued in the absence of efficient proteolytic processing to generate terminally glycosylated gp85 and gp70 proteins. A recombinant FHV containing the FeLV gag and protease genes expressed both gag and gag-protease precursor proteins. Functional protease was produced which mediated the proteolytic maturation of the FeLV gag proteins as in authentic FeLV infection. Use of these recombinant FHVs as live-virus vaccines may provide insight as to the role of specific retroviral proteins in protective immunity. The current use of conventional attenuated FHV vaccines speaks to the wider potential of recombinant FHVs for vaccination in cats.
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Selected References
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- Andrew M. E., Coupar B. E., Boyle D. B., Ada G. L. The roles of influenza virus haemagglutinin and nucleoprotein in protection: analysis using vaccinia virus recombinants. Scand J Immunol. 1987 Jan;25(1):21–28. doi: 10.1111/j.1365-3083.1987.tb01042.x. [DOI] [PubMed] [Google Scholar]
- Bittle J. L., Rubic W. J. Immunogenic and protective effects of the F-2 strain of feline viral rhinotracheitis virus. Am J Vet Res. 1975 Jan;36(1):89–91. [PubMed] [Google Scholar]
- Boshart M., Weber F., Jahn G., Dorsch-Häsler K., Fleckenstein B., Schaffner W. A very strong enhancer is located upstream of an immediate early gene of human cytomegalovirus. Cell. 1985 Jun;41(2):521–530. doi: 10.1016/s0092-8674(85)80025-8. [DOI] [PubMed] [Google Scholar]
- Chakrabarti S., Robert-Guroff M., Wong-Staal F., Gallo R. C., Moss B. Expression of the HTLV-III envelope gene by a recombinant vaccinia virus. Nature. 1986 Apr 10;320(6062):535–537. doi: 10.1038/320535a0. [DOI] [PubMed] [Google Scholar]
- Crandell R. A. Virologic and immunologic aspects of feline viral rhinotracheitis virus. J Am Vet Med Assoc. 1971 Mar 15;158(6 Suppl):922–926. [PubMed] [Google Scholar]
- DUBBS D. R., KIT S. MUTANT STRAINS OF HERPES SIMPLEX DEFICIENT IN THYMIDINE KINASE-INDUCING ACTIVITY. Virology. 1964 Apr;22:493–502. doi: 10.1016/0042-6822(64)90070-4. [DOI] [PubMed] [Google Scholar]
- Debouck C., Gorniak J. G., Strickler J. E., Meek T. D., Metcalf B. W., Rosenberg M. Human immunodeficiency virus protease expressed in Escherichia coli exhibits autoprocessing and specific maturation of the gag precursor. Proc Natl Acad Sci U S A. 1987 Dec;84(24):8903–8906. doi: 10.1073/pnas.84.24.8903. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dewar R. L., Natarajan V., Vasudevachari M. B., Salzman N. P. Synthesis and processing of human immunodeficiency virus type 1 envelope proteins encoded by a recombinant human adenovirus. J Virol. 1989 Jan;63(1):129–136. doi: 10.1128/jvi.63.1.129-136.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dickson C., Atterwill M. Structure and processing of the mouse mammary tumor virus glycoprotein precursor pr73env. J Virol. 1980 Aug;35(2):349–361. doi: 10.1128/jvi.35.2.349-361.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dietzschold B., Wang H. H., Rupprecht C. E., Celis E., Tollis M., Ertl H., Heber-Katz E., Koprowski H. Induction of protective immunity against rabies by immunization with rabies virus ribonucleoprotein. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9165–9169. doi: 10.1073/pnas.84.24.9165. [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]
- Earl P. L., Moss B., Morrison R. P., Wehrly K., Nishio J., Chesebro B. T-lymphocyte priming and protection against Friend leukemia by vaccinia-retrovirus env gene recombinant. Science. 1986 Nov 7;234(4777):728–731. doi: 10.1126/science.3490689. [DOI] [PubMed] [Google Scholar]
- Famulari N. G., Buchhagen D. L., Klenk H. D., Fleissner E. Presence of murine leukemia virus envelope proteins gp70 and p15(E) in a common polyprotein of infected cells. J Virol. 1976 Nov;20(2):501–508. doi: 10.1128/jvi.20.2.501-508.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Foecking M. K., Hofstetter H. Powerful and versatile enhancer-promoter unit for mammalian expression vectors. Gene. 1986;45(1):101–105. doi: 10.1016/0378-1119(86)90137-x. [DOI] [PubMed] [Google Scholar]
- Freed E. O., Myers D. J., Risser R. Mutational analysis of the cleavage sequence of the human immunodeficiency virus type 1 envelope glycoprotein precursor gp160. J Virol. 1989 Nov;63(11):4670–4675. doi: 10.1128/jvi.63.11.4670-4675.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Freed E. O., Risser R. The role of envelope glycoprotein processing in murine leukemia virus infection. J Virol. 1987 Sep;61(9):2852–2856. doi: 10.1128/jvi.61.9.2852-2856.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gheysen D., Jacobs E., de Foresta F., Thiriart C., Francotte M., Thines D., De Wilde M. Assembly and release of HIV-1 precursor Pr55gag virus-like particles from recombinant baculovirus-infected insect cells. Cell. 1989 Oct 6;59(1):103–112. doi: 10.1016/0092-8674(89)90873-8. [DOI] [PubMed] [Google Scholar]
- Gilbert J. H., Pedersen N. C., Nunberg J. H. Feline leukemia virus envelope protein expression encoded by a recombinant vaccinia virus: apparent lack of immunogenicity in vaccinated animals. Virus Res. 1987 Feb;7(1):49–67. doi: 10.1016/0168-1702(87)90057-8. [DOI] [PubMed] [Google Scholar]
- Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
- Grant C. K., Ernisse B. J., Jarrett O., Jones F. R. Feline leukemia virus envelope gp70 of subgroups B and C defined by monoclonal antibodies with cytotoxic and neutralizing functions. J Immunol. 1983 Dec;131(6):3042–3048. [PubMed] [Google Scholar]
- Haley P. J., Hoover E. A., Quackenbush S. L., Gasper P. W., Macy D. W. Influence of antibody infusion on pathogenesis of experimental feline leukemia virus infection. J Natl Cancer Inst. 1985 Apr;74(4):821–827. [PubMed] [Google Scholar]
- Holt C. A., Osorio K., Lilly F. Friend virus-specific cytotoxic T lymphocytes recognize both gag and env gene-encoded specificities. J Exp Med. 1986 Jul 1;164(1):211–226. doi: 10.1084/jem.164.1.211. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hoover E. A., Schaller J. P., Mathes L. E., Olsen R. G. Passive immunity to feline leukemia: evaluation of immunity from dams naturally infected and experimentally vaccinated. Infect Immun. 1977 Apr;16(1):54–59. doi: 10.1128/iai.16.1.54-59.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hu S. L., Kosowski S. G., Dalrymple J. M. Expression of AIDS virus envelope gene in recombinant vaccinia viruses. Nature. 1986 Apr 10;320(6062):537–540. doi: 10.1038/320537a0. [DOI] [PubMed] [Google Scholar]
- Jacobson J. G., Martin S. L., Coen D. M. A conserved open reading frame that overlaps the herpes simplex virus thymidine kinase gene is important for viral growth in cell culture. J Virol. 1989 Apr;63(4):1839–1843. doi: 10.1128/jvi.63.4.1839-1843.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jahn G., Knust E., Schmolla H., Sarre T., Nelson J. A., McDougall J. K., Fleckenstein B. Predominant immediate-early transcripts of human cytomegalovirus AD 169. J Virol. 1984 Feb;49(2):363–370. doi: 10.1128/jvi.49.2.363-370.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jonjić S., del Val M., Keil G. M., Reddehase M. J., Koszinowski U. H. A nonstructural viral protein expressed by a recombinant vaccinia virus protects against lethal cytomegalovirus infection. J Virol. 1988 May;62(5):1653–1658. doi: 10.1128/jvi.62.5.1653-1658.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Karacostas V., Nagashima K., Gonda M. A., Moss B. Human immunodeficiency virus-like particles produced by a vaccinia virus expression vector. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8964–8967. doi: 10.1073/pnas.86.22.8964. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kit S., Kit M., Pirtle E. C. Attenuated properties of thymidine kinase-negative deletion mutant of pseudorabies virus. Am J Vet Res. 1985 Jun;46(6):1359–1367. [PubMed] [Google Scholar]
- Kit S., Qavi H., Gaines J. D., Billingsley P., McConnell S. Thymidine kinase-negative bovine herpesvirus type 1 mutant is stable and highly attenuated in calves. Arch Virol. 1985;86(1-2):63–83. doi: 10.1007/BF01314114. [DOI] [PubMed] [Google Scholar]
- Klavinskis L. S., Whitton J. L., Oldstone M. B. Molecularly engineered vaccine which expresses an immunodominant T-cell epitope induces cytotoxic T lymphocytes that confer protection from lethal virus infection. J Virol. 1989 Oct;63(10):4311–4316. doi: 10.1128/jvi.63.10.4311-4316.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kramer R. A., Schaber M. D., Skalka A. M., Ganguly K., Wong-Staal F., Reddy E. P. HTLV-III gag protein is processed in yeast cells by the virus pol-protease. Science. 1986 Mar 28;231(4745):1580–1584. doi: 10.1126/science.2420008. [DOI] [PubMed] [Google Scholar]
- Lewis M. G., Mathes L. E., Olsen R. G. Protection against feline leukemia by vaccination with a subunit vaccine. Infect Immun. 1981 Dec;34(3):888–894. doi: 10.1128/iai.34.3.888-894.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lowe R. S., Keller P. M., Keech B. J., Davison A. J., Whang Y., Morgan A. J., Kieff E., Ellis R. W. Varicella-zoster virus as a live vector for the expression of foreign genes. Proc Natl Acad Sci U S A. 1987 Jun;84(11):3896–3900. doi: 10.1073/pnas.84.11.3896. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lutz H., Pedersen N. C., Durbin R., Theilen G. H. Monoclonal antibodies to three epitopic regions of feline leukemia virus p27 and their use in enzyme-linked immunosorbent assay of p27. J Immunol Methods. 1983 Jan 28;56(2):209–220. doi: 10.1016/0022-1759(83)90413-1. [DOI] [PubMed] [Google Scholar]
- Mackem S., Roizman B. Differentiation between alpha promoter and regulator regions of herpes simplex virus 1: the functional domains and sequence of a movable alpha regulator. Proc Natl Acad Sci U S A. 1982 Aug;79(16):4917–4921. doi: 10.1073/pnas.79.16.4917. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marchioli C. C., Yancey R. J., Jr, Wardley R. C., Thomsen D. R., Post L. E. A vaccine strain of pseudorabies virus with deletions in the thymidine kinase and glycoprotein X genes. Am J Vet Res. 1987 Nov;48(11):1577–1583. [PubMed] [Google Scholar]
- McCune J. M., Rabin L. B., Feinberg M. B., Lieberman M., Kosek J. C., Reyes G. R., Weissman I. L. Endoproteolytic cleavage of gp160 is required for the activation of human immunodeficiency virus. Cell. 1988 Apr 8;53(1):55–67. doi: 10.1016/0092-8674(88)90487-4. [DOI] [PubMed] [Google Scholar]
- Nam S. H., Kidokoro M., Shida H., Hatanaka M. Processing of gag precursor polyprotein of human T-cell leukemia virus type I by virus-encoded protease. J Virol. 1988 Oct;62(10):3718–3728. doi: 10.1128/jvi.62.10.3718-3728.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nunberg J. H., Rodgers G., Gilbert J. H., Snead R. M. Method to map antigenic determinants recognized by monoclonal antibodies: localization of a determinant of virus neutralization on the feline leukemia virus envelope protein gp70. Proc Natl Acad Sci U S A. 1984 Jun;81(12):3675–3679. doi: 10.1073/pnas.81.12.3675. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nunberg J. H., Wright D. K., Cole G. E., Petrovskis E. A., Post L. E., Compton T., Gilbert J. H. Identification of the thymidine kinase gene of feline herpesvirus: use of degenerate oligonucleotides in the polymerase chain reaction to isolate herpesvirus gene homologs. J Virol. 1989 Aug;63(8):3240–3249. doi: 10.1128/jvi.63.8.3240-3249.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nørregård Nielsen L., Forchhammer J., Dabelsteen E., Jepsen A., Stubbe Teglbjaerg C., Norrild B. Herpes simplex virus-induced changes of the keratin type intermediate filament in rat epithelial cells. J Gen Virol. 1987 Mar;68(Pt 3):737–748. doi: 10.1099/0022-1317-68-3-737. [DOI] [PubMed] [Google Scholar]
- Oroskar A. A., Read G. S. Control of mRNA stability by the virion host shutoff function of herpes simplex virus. J Virol. 1989 May;63(5):1897–1906. doi: 10.1128/jvi.63.5.1897-1906.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pal R., Hoke G. M., Sarngadharan M. G. Role of oligosaccharides in the processing and maturation of envelope glycoproteins of human immunodeficiency virus type 1. Proc Natl Acad Sci U S A. 1989 May;86(9):3384–3388. doi: 10.1073/pnas.86.9.3384. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pedersen N. C., Theilen G. H., Werner L. L. Safety and efficacy studies of live- and killed-feline leukemia virus vaccines. Am J Vet Res. 1979 Aug;40(8):1120–1126. [PubMed] [Google Scholar]
- Perez L. G., Hunter E. Mutations within the proteolytic cleavage site of the Rous sarcoma virus glycoprotein that block processing to gp85 and gp37. J Virol. 1987 May;61(5):1609–1614. doi: 10.1128/jvi.61.5.1609-1614.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Roizman B., Kristie T., McKnight J. L., Michael N., Mavromara-Nazos P., Spector D. The trans-activation of herpes simplex virus gene expression: comparison of two factors and their cis sites. Biochimie. 1988 Aug;70(8):1031–1043. doi: 10.1016/0300-9084(88)90266-0. [DOI] [PubMed] [Google Scholar]
- Rojko J., Essex M., Trainin Z. Feline leukemia/sarcoma viruses and immunodeficiency. Adv Vet Sci Comp Med. 1988;32:57–96. doi: 10.1016/B978-0-12-039232-2.50007-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rota P. A., Maes R. K., Ruyechan W. T. Physical characterization of the genome of feline herpesvirus-1. Virology. 1986 Oct 15;154(1):168–179. doi: 10.1016/0042-6822(86)90439-3. [DOI] [PubMed] [Google Scholar]
- Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
- Sanes J. R., Rubenstein J. L., Nicolas J. F. Use of a recombinant retrovirus to study post-implantation cell lineage in mouse embryos. EMBO J. 1986 Dec 1;5(12):3133–3142. doi: 10.1002/j.1460-2075.1986.tb04620.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schwartzberg P., Colicelli J., Gordon M. L., Goff S. P. Mutations in the gag gene of Moloney murine leukemia virus: effects on production of virions and reverse transcriptase. J Virol. 1984 Mar;49(3):918–924. doi: 10.1128/jvi.49.3.918-924.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shih M. F., Arsenakis M., Tiollais P., Roizman B. Expression of hepatitis B virus S gene by herpes simplex virus type 1 vectors carrying alpha- and beta-regulated gene chimeras. Proc Natl Acad Sci U S A. 1984 Sep;81(18):5867–5870. doi: 10.1073/pnas.81.18.5867. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smiley J. R. Construction in vitro and rescue of a thymidine kinase-deficient deletion mutation of herpes simplex virus. Nature. 1980 May 29;285(5763):333–335. doi: 10.1038/285333a0. [DOI] [PubMed] [Google Scholar]
- Spaete R. R., Mocarski E. S. Regulation of cytomegalovirus gene expression: alpha and beta promoters are trans activated by viral functions in permissive human fibroblasts. J Virol. 1985 Oct;56(1):135–143. doi: 10.1128/jvi.56.1.135-143.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stenberg R. M., Thomsen D. R., Stinski M. F. Structural analysis of the major immediate early gene of human cytomegalovirus. J Virol. 1984 Jan;49(1):190–199. doi: 10.1128/jvi.49.1.190-199.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stewart M. A., Warnock M., Wheeler A., Wilkie N., Mullins J. I., Onions D. E., Neil J. C. Nucleotide sequences of a feline leukemia virus subgroup A envelope gene and long terminal repeat and evidence for the recombinational origin of subgroup B viruses. J Virol. 1986 Jun;58(3):825–834. doi: 10.1128/jvi.58.3.825-834.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tatarov G. Apathogener Mutant des Aujeszky-Virus, induziert von 5-Jodo-2-Deoxyuridin (JUDR) Zentralbl Veterinarmed B. 1968 Oct;15(8):847–853. [PubMed] [Google Scholar]
- Thomsen D. R., Marotti K. R., Palermo D. P., Post L. E. Pseudorabies virus as a live virus vector for expression of foreign genes. Gene. 1987;57(2-3):261–265. doi: 10.1016/0378-1119(87)90130-2. [DOI] [PubMed] [Google Scholar]
- Whealy M. E., Baumeister K., Robbins A. K., Enquist L. W. A herpesvirus vector for expression of glycosylated membrane antigens: fusion proteins of pseudorabies virus gIII and human immunodeficiency virus type 1 envelope glycoproteins. J Virol. 1988 Nov;62(11):4185–4194. doi: 10.1128/jvi.62.11.4185-4194.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wills J. W., Srinivas R. V., Hunter E. Mutations of the Rous sarcoma virus env gene that affect the transport and subcellular location of the glycoprotein products. J Cell Biol. 1984 Dec;99(6):2011–2023. doi: 10.1083/jcb.99.6.2011. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yoshinaka Y., Katoh I., Copeland T. D., Oroszlan S. Translational readthrough of an amber termination codon during synthesis of feline leukemia virus protease. J Virol. 1985 Sep;55(3):870–873. doi: 10.1128/jvi.55.3.870-873.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- de Noronha F., Schäfer W., Essex M., Bolognesi D. P. Influence of antisera to oncornavirus glycoprotein (gp71) on infections of cats with feline leukemia virus. Virology. 1978 Apr;85(2):617–621. doi: 10.1016/0042-6822(78)90467-1. [DOI] [PubMed] [Google Scholar]
- van Drunen Littel-van den Hurk S., Zamb T., Babiuk L. A. Synthesis, cellular location, and immunogenicity of bovine herpesvirus 1 glycoproteins gI and gIII expressed by recombinant vaccinia virus. J Virol. 1989 May;63(5):2159–2168. doi: 10.1128/jvi.63.5.2159-2168.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]