Abstract
Aleutian mink disease parvovirus (ADV) infection causes both acute and chronic disease in mink, and we have previously shown that it is the level of viral gene expression that determines the disease pattern. To study the gene regulation of ADV, we have cloned the P3 ADV and P36 ADV promoters in front of a reporter gene, the chloramphenicol acetyltransferase (CAT) gene, and analyzed these constructs by transient transfection in a feline kidney cell line and mouse NIH 3T3 cells. The genes for ADV structural proteins (VP1 and VP2) and the nonstructural proteins (NS-1, NS-2, and NS-3) were cloned into a eukaryotic expression vector, and their functions in regulation of the P3 ADV and P36 ADV promoters were examined in cotransfection experiments. The ADV NS-1 protein was able to transactivate the P36 ADV promoter and, to a lesser degree, the P3 ADV promoter. Constitutive activities of the P3 ADV and P36 ADV promoters were weaker than those of the corresponding promoters from the prototypic parvovirus minute virus of mice (MVM) and canine parvovirus (CPV). Also, the level of transactivation of the P36 ADV promoter was much lower than those of the corresponding P38 MVM and P38 CPV promoters transactivated with MVM NS-1. Moreover, the ADV NS-1 gene product could transactivate the P38 MVM promoter to higher levels than it could transactivate the P36 ADV promoter, while the P36 ADV promoter could be transactivated by MVM NS-1 and ADV NS-1 to similar levels. Taken together, these data indicated that cis-acting sequences in the P36 ADV promoter play a major role in determining the low level of transactivation observed. The P3 ADV and P4 MVM promoters could be transactivated to some degree by their respective NS-1 gene products. However, in contrast to the situation for the late promoters, switching NS-1 proteins between the two viruses was not possible. This finding may indicate a different mechanism of transactivation of the early promoters (P3 ADV and P4 MVM) compared with the late (P36 ADV and P38 MVM) promoters. In summary, the constitutive levels of expression from the ADV promoters are weaker than the levels from the corresponding promoters of MVM and CPV. Moreover, the level of NS-1-mediated transactivation of the late ADV promoter is impaired compared with the level of transactivation of the late promoters of MVM and CPV.(ABSTRACT TRUNCATED AT 400 WORDS)
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- Aasted B., Alexandersen S., Hansen M. Treatment of neonatally Aleutian disease virus (ADV) infected mink kits with gammaglobulin containing antibodies to ADV reduces the death rate of mink kits. Acta Vet Scand. 1988;29(3-4):323–330. doi: 10.1186/BF03548625. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Aasted B., Leslie R. G. Virus-specific B-lymphocytes are probably the primary targets for Aleutian disease virus. Vet Immunol Immunopathol. 1991 Apr;28(2):127–141. doi: 10.1016/0165-2427(91)90135-y. [DOI] [PubMed] [Google Scholar]
- Ahn J. K., Gavin B. J., Kumar G., Ward D. C. Transcriptional analysis of minute virus of mice P4 promoter mutants. J Virol. 1989 Dec;63(12):5425–5439. doi: 10.1128/jvi.63.12.5425-5439.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ahn J. K., Pitluk Z. W., Ward D. C. The GC box and TATA transcription control elements in the P38 promoter of the minute virus of mice are necessary and sufficient for transactivation by the nonstructural protein NS1. J Virol. 1992 Jun;66(6):3776–3783. doi: 10.1128/jvi.66.6.3776-3783.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Alexandersen S. Acute interstitial pneumonia in mink kits: experimental reproduction of the disease. Vet Pathol. 1986 Sep;23(5):579–588. doi: 10.1177/030098588602300506. [DOI] [PubMed] [Google Scholar]
- Alexandersen S., Bloom M. E., Perryman S. Detailed transcription map of Aleutian mink disease parvovirus. J Virol. 1988 Oct;62(10):3684–3694. doi: 10.1128/jvi.62.10.3684-3694.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Alexandersen S., Bloom M. E. Studies on the sequential development of acute interstitial pneumonia caused by Aleutian disease virus in mink kits. J Virol. 1987 Jan;61(1):81–86. doi: 10.1128/jvi.61.1.81-86.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Alexandersen S., Bloom M. E., Wolfinbarger J. Evidence of restricted viral replication in adult mink infected with Aleutian disease of mink parvovirus. J Virol. 1988 May;62(5):1495–1507. doi: 10.1128/jvi.62.5.1495-1507.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Alexandersen S., Bloom M. E., Wolfinbarger J., Race R. E. In situ molecular hybridization for detection of Aleutian mink disease parvovirus DNA by using strand-specific probes: identification of target cells for viral replication in cell cultures and in mink kits with virus-induced interstitial pneumonia. J Virol. 1987 Aug;61(8):2407–2419. doi: 10.1128/jvi.61.8.2407-2419.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Alexandersen S., Carpenter S. Characterization of variable regions in the envelope and S3 open reading frame of equine infectious anemia virus. J Virol. 1991 Aug;65(8):4255–4262. doi: 10.1128/jvi.65.8.4255-4262.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Alexandersen S., Larsen S., Cohn A., Uttenthal A., Race R. E., Aasted B., Hansen M., Bloom M. E. Passive transfer of antiviral antibodies restricts replication of Aleutian mink disease parvovirus in vivo. J Virol. 1989 Jan;63(1):9–17. doi: 10.1128/jvi.63.1.9-17.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Alexandersen S. Pathogenesis of disease caused by Aleutian mink disease parvovirus. APMIS Suppl. 1990;14:1–32. [PubMed] [Google Scholar]
- Alexandersen S., Uttenthal-Jensen A., Aasted B. Demonstration of non-degraded Aleutian disease virus (ADV) proteins in lung tissue from experimentally infected mink kits. Brief report. Arch Virol. 1986;87(1-2):127–133. doi: 10.1007/BF01310549. [DOI] [PubMed] [Google Scholar]
- Ben-Asher E., Aloni Y. Transcription of minute virus of mice, an autonomous parvovirus, may be regulated by attenuation. J Virol. 1984 Oct;52(1):266–276. doi: 10.1128/jvi.52.1.266-276.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bensimhon M., Gabarro-Arpa J., Ehrlich R., Reiss C. Physical characteristics in eucaryotic promoters. Nucleic Acids Res. 1983 Jul 11;11(13):4521–4540. doi: 10.1093/nar/11.13.4521. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Berns K. I., Labow M. A. Parvovirus gene regulation. J Gen Virol. 1987 Mar;68(Pt 3):601–614. doi: 10.1099/0022-1317-68-3-601. [DOI] [PubMed] [Google Scholar]
- Bloom M. E., Alexandersen S., Perryman S., Lechner D., Wolfinbarger J. B. Nucleotide sequence and genomic organization of Aleutian mink disease parvovirus (ADV): sequence comparisons between a nonpathogenic and a pathogenic strain of ADV. J Virol. 1988 Aug;62(8):2903–2915. doi: 10.1128/jvi.62.8.2903-2915.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bloom M. E. Parvovirus infections: features reminiscent of AIDS. Ann N Y Acad Sci. 1984;437:110–120. doi: 10.1111/j.1749-6632.1984.tb37128.x. [DOI] [PubMed] [Google Scholar]
- Bloom M. E., Race R. E., Wolfinbarger J. B. Analysis of Aleutian disease of mink parvovirus infection using strand-specific hybridization probes. Intervirology. 1987;27(2):102–111. doi: 10.1159/000149727. [DOI] [PubMed] [Google Scholar]
- Bloom M. E., Race R. E., Wolfinbarger J. B. Characterization of Aleutian disease virus as a parvovirus. J Virol. 1980 Sep;35(3):836–843. doi: 10.1128/jvi.35.3.836-843.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brandenburger A., Legendre D., Avalosse B., Rommelaere J. NS-1 and NS-2 proteins may act synergistically in the cytopathogenicity of parvovirus MVMp. Virology. 1990 Feb;174(2):576–584. doi: 10.1016/0042-6822(90)90110-d. [DOI] [PubMed] [Google Scholar]
- Carpenter S., Alexandersen S., Long M. J., Perryman S., Chesebro B. Identification of a hypervariable region in the long terminal repeat of equine infectious anemia virus. J Virol. 1991 Mar;65(3):1605–1610. doi: 10.1128/jvi.65.3.1605-1610.1991. [DOI] [PMC free article] [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]
- Christensen J., Storgaard T., Bloch B., Alexandersen S., Aasted B. Expression of Aleutian mink disease parvovirus proteins in a baculovirus vector system. J Virol. 1993 Jan;67(1):229–238. doi: 10.1128/jvi.67.1.229-238.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clemens K. E., Cerutis D. R., Burger L. R., Yang C. Q., Pintel D. J. Cloning of minute virus of mice cDNAs and preliminary analysis of individual viral proteins expressed in murine cells. J Virol. 1990 Aug;64(8):3967–3973. doi: 10.1128/jvi.64.8.3967-3973.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clemens K. E., Pintel D. J. The two transcription units of the autonomous parvovirus minute virus of mice are transcribed in a temporal order. J Virol. 1988 Apr;62(4):1448–1451. doi: 10.1128/jvi.62.4.1448-1451.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cotmore S. F., Tattersall P. The autonomously replicating parvoviruses of vertebrates. Adv Virus Res. 1987;33:91–174. doi: 10.1016/s0065-3527(08)60317-6. [DOI] [PubMed] [Google Scholar]
- Doerig C., Hirt B., Antonietti J. P., Beard P. Nonstructural protein of parvoviruses B19 and minute virus of mice controls transcription. J Virol. 1990 Jan;64(1):387–396. doi: 10.1128/jvi.64.1.387-396.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Doerig C., Hirt B., Beard P., Antonietti J. P. Minute virus of mice non-structural protein NS-1 is necessary and sufficient for trans-activation of the viral P39 promoter. J Gen Virol. 1988 Oct;69(Pt 10):2563–2573. doi: 10.1099/0022-1317-69-10-2563. [DOI] [PubMed] [Google Scholar]
- Gavin B. J., Ward D. C. Positive and negative regulation of the minute virus of mice P38 promoter. J Virol. 1990 May;64(5):2057–2063. doi: 10.1128/jvi.64.5.2057-2063.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gottschalck E., Alexandersen S., Cohn A., Poulsen L. A., Bloom M. E., Aasted B. Nucleotide sequence analysis of Aleutian mink disease parvovirus shows that multiple virus types are present in infected mink. J Virol. 1991 Aug;65(8):4378–4386. doi: 10.1128/jvi.65.8.4378-4386.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gu M. L., Chen F. X., Rhode S. L. Parvovirus H-1 P38 promoter requires the trans-activation region (tar), an SP1 site, and a TATA box for full activity. Virology. 1992 Mar;187(1):10–17. doi: 10.1016/0042-6822(92)90290-6. [DOI] [PubMed] [Google Scholar]
- Hanson N. D., Rhode S. L., 3rd Parvovirus NS1 stimulates P4 expression by interaction with the terminal repeats and through DNA amplification. J Virol. 1991 Aug;65(8):4325–4333. doi: 10.1128/jvi.65.8.4325-4333.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Im D. S., Muzyczka N. The AAV origin binding protein Rep68 is an ATP-dependent site-specific endonuclease with DNA helicase activity. Cell. 1990 May 4;61(3):447–457. doi: 10.1016/0092-8674(90)90526-k. [DOI] [PubMed] [Google Scholar]
- Jongeneel C. V., Sahli R., McMaster G. K., Hirt B. A precise map of splice junctions in the mRNAs of minute virus of mice, an autonomous parvovirus. J Virol. 1986 Sep;59(3):564–573. doi: 10.1128/jvi.59.3.564-573.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kaaden O. R., Haas L., Löchelt M., Roth S. Replication of Aleutian disease virus in mink lymphocytes infected in vitro. Intervirology. 1986;25(4):201–209. doi: 10.1159/000149676. [DOI] [PubMed] [Google Scholar]
- Klein-Bauernschmitt P., zur Hausen H., Schlehofer J. R. Induction of differentiation-associated changes in established human cells by infection with adeno-associated virus type 2. J Virol. 1992 Jul;66(7):4191–4200. doi: 10.1128/jvi.66.7.4191-4200.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Larsen S., Alexandersen S., Lund E., Have P., Hansen M. Acute interstitial pneumonitis caused by Aleutian disease virus in mink kits. Acta Pathol Microbiol Immunol Scand A. 1984 Sep;92(5):391–393. doi: 10.1111/j.1699-0463.1984.tb04419.x. [DOI] [PubMed] [Google Scholar]
- Li X., Rhode S. L., 3rd Mutation of lysine 405 to serine in the parvovirus H-1 NS1 abolishes its functions for viral DNA replication, late promoter trans activation, and cytotoxicity. J Virol. 1990 Oct;64(10):4654–4660. doi: 10.1128/jvi.64.10.4654-4660.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Li X., Rhode S. L., 3rd Nonstructural protein NS2 of parvovirus H-1 is required for efficient viral protein synthesis and virus production in rat cells in vivo and in vitro. Virology. 1991 Sep;184(1):117–130. doi: 10.1016/0042-6822(91)90828-y. [DOI] [PubMed] [Google Scholar]
- Mori S., Wolfinbarger J. B., Dowling N., Wei W., Bloom M. E. Simultaneous identification of viral proteins and nucleic acids in cells infected with Aleutian mink disease parvovirus. Microb Pathog. 1990 Oct;9(4):243–253. doi: 10.1016/0882-4010(90)90013-g. [DOI] [PubMed] [Google Scholar]
- Mori S., Wolfinbarger J. B., Miyazawa M., Bloom M. E. Replication of Aleutian mink disease parvovirus in lymphoid tissues of adult mink: involvement of follicular dendritic cells and macrophages. J Virol. 1991 Feb;65(2):952–956. doi: 10.1128/jvi.65.2.952-956.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mortimer P. P., Humphries R. K., Moore J. G., Purcell R. H., Young N. S. A human parvovirus-like virus inhibits haematopoietic colony formation in vitro. 1983 Mar 31-Apr 6Nature. 302(5907):426–429. doi: 10.1038/302426a0. [DOI] [PubMed] [Google Scholar]
- Naeger L. K., Cater J., Pintel D. J. The small nonstructural protein (NS2) of the parvovirus minute virus of mice is required for efficient DNA replication and infectious virus production in a cell-type-specific manner. J Virol. 1990 Dec;64(12):6166–6175. doi: 10.1128/jvi.64.12.6166-6175.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ozawa K., Ayub J., Kajigaya S., Shimada T., Young N. The gene encoding the nonstructural protein of B19 (human) parvovirus may be lethal in transfected cells. J Virol. 1988 Aug;62(8):2884–2889. doi: 10.1128/jvi.62.8.2884-2889.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Parrish C. R., Aquadro C. F., Carmichael L. E. Canine host range and a specific epitope map along with variant sequences in the capsid protein gene of canine parvovirus and related feline, mink, and raccoon parvoviruses. Virology. 1988 Oct;166(2):293–307. doi: 10.1016/0042-6822(88)90500-4. [DOI] [PubMed] [Google Scholar]
- Parrish C. R., Carmichael L. E., Antczak D. F. Antigenic relationships between canine parvovirus type 2, feline panleukopenia virus and mink enteritis virus using conventional antisera and monoclonal antibodies. Arch Virol. 1982;72(4):267–278. doi: 10.1007/BF01315223. [DOI] [PubMed] [Google Scholar]
- Parrish C. R., Carmichael L. E. Antigenic structure and variation of canine parvovirus type-2, feline panleukopenia virus, and mink enteritis virus. Virology. 1983 Sep;129(2):401–414. doi: 10.1016/0042-6822(83)90179-4. [DOI] [PubMed] [Google Scholar]
- Parrish C. R. Emergence, natural history, and variation of canine, mink, and feline parvoviruses. Adv Virus Res. 1990;38:403–450. doi: 10.1016/S0065-3527(08)60867-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Parrish C. R., Gorham J. R., Schwartz T. M., Carmichael L. E. Characterization of antigenic variation among mink enteritis virus isolates. Am J Vet Res. 1984 Dec;45(12):2591–2599. [PubMed] [Google Scholar]
- Parrish C. R., Leathers C. W., Pearson R., Gorham J. R. Comparisons of feline panleukopenia virus, canine parvovirus, raccoon parvovirus, and mink enteritis virus and their pathogenicity for mink and ferrets. Am J Vet Res. 1987 Oct;48(10):1429–1435. [PubMed] [Google Scholar]
- Porter D. D. Aleutian disease: a persistent parvovirus infection of mink with a maximal but ineffective host humoral immune response. Prog Med Virol. 1986;33:42–60. [PubMed] [Google Scholar]
- Porter D. D., Larsen A. E., Cox N. A., Porter H. G., Suffin S. C. Isolation of Aleutian disease virus of mink in cell culture. Intervirology. 1977;8(3):129–144. doi: 10.1159/000148888. [DOI] [PubMed] [Google Scholar]
- Porter D. D., Larsen A. E., Porter H. G. The pathogenesis of Aleutian disease of mink. I. In vivo viral replication and the host antibody response to viral antigen. J Exp Med. 1969 Sep 1;130(3):575–593. doi: 10.1084/jem.130.3.575. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rhode S. L., 3rd, Richard S. M. Characterization of the trans-activation-responsive element of the parvovirus H-1 P38 promoter. J Virol. 1987 Sep;61(9):2807–2815. doi: 10.1128/jvi.61.9.2807-2815.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rhode S. L., 3rd trans-Activation of parvovirus P38 promoter by the 76K noncapsid protein. J Virol. 1985 Sep;55(3):886–889. doi: 10.1128/jvi.55.3.886-889.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rommelaere J., Cornelis J. J. Antineoplastic activity of parvoviruses. J Virol Methods. 1991 Aug;33(3):233–251. doi: 10.1016/0166-0934(91)90024-t. [DOI] [PubMed] [Google Scholar]
- Schoborg R. V., Pintel D. J. Accumulation of MVM gene products is differentially regulated by transcription initiation, RNA processing and protein stability. Virology. 1991 Mar;181(1):22–34. doi: 10.1016/0042-6822(91)90466-o. [DOI] [PubMed] [Google Scholar]
- Siegl G., Bates R. C., Berns K. I., Carter B. J., Kelly D. C., Kurstak E., Tattersall P. Characteristics and taxonomy of Parvoviridae. Intervirology. 1985;23(2):61–73. doi: 10.1159/000149587. [DOI] [PubMed] [Google Scholar]
- Storgaard T., Christensen J., Aasted B., Alexandersen S. cis-acting sequences in the Aleutian mink disease parvovirus late promoter important for transcription: comparison to the canine parvovirus and minute virus of mice. J Virol. 1993 Apr;67(4):1887–1895. doi: 10.1128/jvi.67.4.1887-1895.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Uttenthal A., Larsen S., Lund E., Bloom M. E., Storgård T., Alexandersen S. Analysis of experimental mink enteritis virus infection in mink: in situ hybridization, serology, and histopathology. J Virol. 1990 Jun;64(6):2768–2779. doi: 10.1128/jvi.64.6.2768-2779.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van Rooijen N. Follicular dendritic cell-B cell interactions in virus disease. Common localization but different cell damage caused by antibody immobilized virus? Arch Virol. 1992;122(1-2):215–218. doi: 10.1007/BF01321130. [DOI] [PubMed] [Google Scholar]