Abstract
The bovine immunodeficiency virus (BIV) gag gene encodes a 53-kDa precursor (Pr53gag) that is involved in virus particle assembly and is further processed into the putative matrix (MA), capsid (CA), and nucleocapsid (NC) functional domains in the mature virus. Gag determinants are also found in the Gag-Pol polyprotein precursor. To immunologically identify the major precursors and processed products of the BIV gag gene, monospecific rabbit sera to recombinant BIV MA protein and Pr53gag and peptides predicted to correspond to the CA and NC proteins and the MA-CA cleavage site were developed and used in immunoprecipitations and immunoblots of BIV antigens. Monospecific antisera to native and recombinant human immunodeficiency virus type 1 proteins were also used to identify analogous BIV Gag proteins and to determine whether cross-reactive epitopes were present in the BIV Gag precursors or processed products. The BIV MA, CA, and NC Gag proteins were identified as p16, p26, and p13, respectively. In addition to BIV Pr53gag, the major Gag precursor, two other Gag-related precursors of 170 and 49 kDa were identified that have been designated pPr170gag-pol and Pr49gag, respectively; pPr170gag-pol is the Gag-Pol polyprotein precursor, and Pr49gag is the transframe Gag precursor present in pPr170gag-pol. Several alternative Gag cleavage products were also observed, including p23, which contains CA and NC determinants, and p10, which contains a peptide sequence conserved in the CA proteins of most lentiviruses. The monospecific antisera to human immunodeficiency virus type 1 CA (p24) and NC (p7) proteins showed cross-reactivity to and aided in the identification of analogous BIV proteins. Based on the present data, a scheme for the processing of BIV Gag precursors is proposed.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Baron M. H., Baltimore D. Antibodies against the chemically synthesized genome-linked protein of poliovirus react with native virus-specific proteins. Cell. 1982 Feb;28(2):395–404. doi: 10.1016/0092-8674(82)90357-9. [DOI] [PubMed] [Google Scholar]
- Benton C. V., Hodge H. M., Fine D. L. Comparative large-scale propagation of retroviruses from Old World (Mason-Pfizer monkey virus) and New World (squirrel monkey virus) primates. In Vitro. 1978 Feb;14(2):192–199. doi: 10.1007/BF02618222. [DOI] [PubMed] [Google Scholar]
- Braun M. J., Lahn S., Boyd A. L., Kost T. A., Nagashima K., Gonda M. A. Molecular cloning of biologically active proviruses of bovine immunodeficiency-like virus. Virology. 1988 Dec;167(2):515–523. [PubMed] [Google Scholar]
- Carpenter S., Miller L. D., Alexandersen S., Whetstone C. A., VanDerMaaten M. J., Viuff B., Wannemuehler Y., Miller J. M., Roth J. A. Characterization of early pathogenic effects after experimental infection of calves with bovine immunodeficiency-like virus. J Virol. 1992 Feb;66(2):1074–1083. doi: 10.1128/jvi.66.2.1074-1083.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chamorro M., Parkin N., Varmus H. E. An RNA pseudoknot and an optimal heptameric shift site are required for highly efficient ribosomal frameshifting on a retroviral messenger RNA. Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):713–717. doi: 10.1073/pnas.89.2.713. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gardner M. B., Luciw P. A. Animal models of AIDS. FASEB J. 1989 Dec;3(14):2593–2606. doi: 10.1096/fasebj.3.14.2556312. [DOI] [PubMed] [Google Scholar]
- Garvey K. J., Oberste M. S., Elser J. E., Braun M. J., Gonda M. A. Nucleotide sequence and genome organization of biologically active proviruses of the bovine immunodeficiency-like virus. Virology. 1990 Apr;175(2):391–409. doi: 10.1016/0042-6822(90)90424-p. [DOI] [PubMed] [Google Scholar]
- Gonda M. A., Braun M. J., Carter S. G., Kost T. A., Bess J. W., Jr, Arthur L. O., Van der Maaten M. J. Characterization and molecular cloning of a bovine lentivirus related to human immunodeficiency virus. 1987 Nov 26-Dec 2Nature. 330(6146):388–391. doi: 10.1038/330388a0. [DOI] [PubMed] [Google Scholar]
- Gonda M. A., Oberste M. S., Garvey K. J., Pallansch L. A., Battles J. K., Pifat D. Y., Bess J. W., Jr, Nagashima K. Development of the bovine immunodeficiency-like virus as a model of lentivirus disease. Dev Biol Stand. 1990;72:97–110. [PubMed] [Google Scholar]
- Göttlinger H. G., Dorfman T., Sodroski J. G., Haseltine W. A. Effect of mutations affecting the p6 gag protein on human immunodeficiency virus particle release. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3195–3199. doi: 10.1073/pnas.88.8.3195. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Göttlinger H. G., Sodroski J. G., Haseltine W. A. Role of capsid precursor processing and myristoylation in morphogenesis and infectivity of human immunodeficiency virus type 1. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5781–5785. doi: 10.1073/pnas.86.15.5781. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Henderson L. E., Benveniste R. E., Sowder R., Copeland T. D., Schultz A. M., Oroszlan S. Molecular characterization of gag proteins from simian immunodeficiency virus (SIVMne). J Virol. 1988 Aug;62(8):2587–2595. doi: 10.1128/jvi.62.8.2587-2595.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Henderson L. E., Bowers M. A., Sowder R. C., 2nd, Serabyn S. A., Johnson D. G., Bess J. W., Jr, Arthur L. O., Bryant D. K., Fenselau C. Gag proteins of the highly replicative MN strain of human immunodeficiency virus type 1: posttranslational modifications, proteolytic processings, and complete amino acid sequences. J Virol. 1992 Apr;66(4):1856–1865. doi: 10.1128/jvi.66.4.1856-1865.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Henderson L. E., Sowder R. C., Smythers G. W., Oroszlan S. Chemical and immunological characterizations of equine infectious anemia virus gag-encoded proteins. J Virol. 1987 Apr;61(4):1116–1124. doi: 10.1128/jvi.61.4.1116-1124.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Henderson L. E., Sowder R., Copeland T. D., Smythers G., Oroszlan S. Quantitative separation of murine leukemia virus proteins by reversed-phase high-pressure liquid chromatography reveals newly described gag and env cleavage products. J Virol. 1984 Nov;52(2):492–500. doi: 10.1128/jvi.52.2.492-500.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hizi A., Hughes S. H. Expression of the Moloney murine leukemia virus and human immunodeficiency virus integration proteins in Escherichia coli. Virology. 1988 Dec;167(2):634–638. [PubMed] [Google Scholar]
- Hizi A., McGill C., Hughes S. H. Expression of soluble, enzymatically active, human immunodeficiency virus reverse transcriptase in Escherichia coli and analysis of mutants. Proc Natl Acad Sci U S A. 1988 Feb;85(4):1218–1222. doi: 10.1073/pnas.85.4.1218. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Horzinek M., Keldermans L., Stuurman T., Black J., Herrewegh A., Sillekens P., Koolen M. Bovine immunodeficiency virus: immunochemical characterization and serological survey. J Gen Virol. 1991 Dec;72(Pt 12):2923–2928. doi: 10.1099/0022-1317-72-12-2923. [DOI] [PubMed] [Google Scholar]
- Hussain K. A., Issel C. J., Rwambo P. M., Arnizaut A. B., Ball J. M., Schnorr K. L., Montelaro R. C. Identification of gag precursor of equine infectious anaemia virus with monoclonal antibodies to the major viral core protein, p26. J Gen Virol. 1988 Jul;69(Pt 7):1719–1724. doi: 10.1099/0022-1317-69-7-1719. [DOI] [PubMed] [Google Scholar]
- Jacks T., Power M. D., Masiarz F. R., Luciw P. A., Barr P. J., Varmus H. E. Characterization of ribosomal frameshifting in HIV-1 gag-pol expression. Nature. 1988 Jan 21;331(6153):280–283. doi: 10.1038/331280a0. [DOI] [PubMed] [Google Scholar]
- Jacks T., Varmus H. E. Expression of the Rous sarcoma virus pol gene by ribosomal frameshifting. Science. 1985 Dec 13;230(4731):1237–1242. doi: 10.1126/science.2416054. [DOI] [PubMed] [Google Scholar]
- Jamjoom G. A., Naso R. B., Arlinghaus R. B. Further characterization of intracellular precursor polyproteins of Rauscher leukemia virus. Virology. 1977 May 1;78(1):11–34. doi: 10.1016/0042-6822(77)90075-7. [DOI] [PubMed] [Google Scholar]
- Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
- Leis J., Baltimore D., Bishop J. M., Coffin J., Fleissner E., Goff S. P., Oroszlan S., Robinson H., Skalka A. M., Temin H. M. Standardized and simplified nomenclature for proteins common to all retroviruses. J Virol. 1988 May;62(5):1808–1809. doi: 10.1128/jvi.62.5.1808-1809.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lillehoj E. P., Salazar F. H., Mervis R. J., Raum M. G., Chan H. W., Ahmad N., Venkatesan S. Purification and structural characterization of the putative gag-pol protease of human immunodeficiency virus. J Virol. 1988 Aug;62(8):3053–3058. doi: 10.1128/jvi.62.8.3053-3058.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mervis R. J., Ahmad N., Lillehoj E. P., Raum M. G., Salazar F. H., Chan H. W., Venkatesan S. The gag gene products of human immunodeficiency virus type 1: alignment within the gag open reading frame, identification of posttranslational modifications, and evidence for alternative gag precursors. J Virol. 1988 Nov;62(11):3993–4002. doi: 10.1128/jvi.62.11.3993-4002.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Oberste M. S., Greenwood J. D., Gonda M. A. Analysis of the transcription pattern and mapping of the putative rev and env splice junctions of bovine immunodeficiency-like virus. J Virol. 1991 Jul;65(7):3932–3937. doi: 10.1128/jvi.65.7.3932-3937.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pifat D. Y., Ennis W. H., Ward J. M., Oberste M. S., Gonda M. A. Persistent infection of rabbits with bovine immunodeficiency-like virus. J Virol. 1992 Jul;66(7):4518–4524. doi: 10.1128/jvi.66.7.4518-4524.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rasmussen L., Battles J. K., Ennis W. H., Nagashima K., Gonda M. A. Characterization of virus-like particles produced by a recombinant baculovirus containing the gag gene of the bovine immunodeficiency-like virus. Virology. 1990 Oct;178(2):435–451. doi: 10.1016/0042-6822(90)90341-n. [DOI] [PubMed] [Google Scholar]
- Rasmussen L., Greenwood J. D., Gonda M. A. Expression of bovine immunodeficiency-like virus envelope glycoproteins by a recombinant baculovirus in insect cells. Virology. 1992 Feb;186(2):551–561. doi: 10.1016/0042-6822(92)90021-g. [DOI] [PubMed] [Google Scholar]
- Ratner L., Haseltine W., Patarca R., Livak K. J., Starcich B., Josephs S. F., Doran E. R., Rafalski J. A., Whitehorn E. A., Baumeister K. Complete nucleotide sequence of the AIDS virus, HTLV-III. Nature. 1985 Jan 24;313(6000):277–284. doi: 10.1038/313277a0. [DOI] [PubMed] [Google Scholar]
- Rein A., McClure M. R., Rice N. R., Luftig R. B., Schultz A. M. Myristylation site in Pr65gag is essential for virus particle formation by Moloney murine leukemia virus. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7246–7250. doi: 10.1073/pnas.83.19.7246. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Robey W. G., Safai B., Oroszlan S., Arthur L. O., Gonda M. A., Gallo R. C., Fischinger P. J. Characterization of envelope and core structural gene products of HTLV-III with sera from AIDS patients. Science. 1985 May 3;228(4699):593–595. doi: 10.1126/science.2984774. [DOI] [PubMed] [Google Scholar]
- Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schultz A. M., Henderson L. E., Oroszlan S. Fatty acylation of proteins. Annu Rev Cell Biol. 1988;4:611–647. doi: 10.1146/annurev.cb.04.110188.003143. [DOI] [PubMed] [Google Scholar]
- Schwartz D. E., Tizard R., Gilbert W. Nucleotide sequence of Rous sarcoma virus. Cell. 1983 Mar;32(3):853–869. doi: 10.1016/0092-8674(83)90071-5. [DOI] [PubMed] [Google Scholar]
- Seelmeier S., Schmidt H., Turk V., von der Helm K. Human immunodeficiency virus has an aspartic-type protease that can be inhibited by pepstatin A. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6612–6616. doi: 10.1073/pnas.85.18.6612. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Van der Maaten M. J., Boothe A. D., Seger C. L. Isolation of a virus from cattle with persistent lymphocytosis. J Natl Cancer Inst. 1972 Dec;49(6):1649–1657. doi: 10.1093/jnci/49.6.1649. [DOI] [PubMed] [Google Scholar]
- Varmus H. Retroviruses. Science. 1988 Jun 10;240(4858):1427–1435. doi: 10.1126/science.3287617. [DOI] [PubMed] [Google Scholar]
- Veronese F. D., Copeland T. D., Oroszlan S., Gallo R. C., Sarngadharan M. G. Biochemical and immunological analysis of human immunodeficiency virus gag gene products p17 and p24. J Virol. 1988 Mar;62(3):795–801. doi: 10.1128/jvi.62.3.795-801.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Veronese F. D., Rahman R., Copeland T. D., Oroszlan S., Gallo R. C., Sarngadharan M. G. Immunological and chemical analysis of P6, the carboxyl-terminal fragment of HIV P15. AIDS Res Hum Retroviruses. 1987 Fall;3(3):253–264. doi: 10.1089/aid.1987.3.253. [DOI] [PubMed] [Google Scholar]
- Wain-Hobson S., Sonigo P., Danos O., Cole S., Alizon M. Nucleotide sequence of the AIDS virus, LAV. Cell. 1985 Jan;40(1):9–17. doi: 10.1016/0092-8674(85)90303-4. [DOI] [PubMed] [Google Scholar]
- Whetstone C. A., VanDerMaaten M. J., Black J. W. Humoral immune response to the bovine immunodeficiency-like virus in experimentally and naturally infected cattle. J Virol. 1990 Jul;64(7):3557–3561. doi: 10.1128/jvi.64.7.3557-3561.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Whetstone C. A., VanDerMaaten M. J., Miller J. M. A western blot assay for the detection of antibodies to bovine immunodeficiency-like virus in experimentally inoculated cattle, sheep, and goats. Arch Virol. 1991;116(1-4):119–131. doi: 10.1007/BF01319236. [DOI] [PubMed] [Google Scholar]
- Yoshinaka Y., Katoh I., Copeland T. D., Oroszlan S. Murine leukemia virus protease is encoded by the gag-pol gene and is synthesized through suppression of an amber termination codon. Proc Natl Acad Sci U S A. 1985 Mar;82(6):1618–1622. doi: 10.1073/pnas.82.6.1618. [DOI] [PMC free article] [PubMed] [Google Scholar]
- ten Dam E. B., Pleij C. W., Bosch L. RNA pseudoknots: translational frameshifting and readthrough on viral RNAs. Virus Genes. 1990 Jul;4(2):121–136. doi: 10.1007/BF00678404. [DOI] [PMC free article] [PubMed] [Google Scholar]