Abstract
We have recently shown that the envelope glycoprotein of the ROD10 isolate of human immunodeficiency virus type 2 (HIV-2) has the ability to positively regulate HIV-2 viral particle release. The activity provided by the ROD10 Env was remarkably similar to that of the HIV-1 Vpu protein, thus raising the possibility that the two proteins act in a related fashion. We now show that the ROD10 Env can functionally replace Vpu to enhance the rate of HIV-1 particle release. When provided in trans, both Vpu and the ROD10 Env restored wild-type levels of particle release in a Vpu-deficient mutant of the NL4-3 molecular clone with indistinguishable efficiencies. This effect was independent of the presence of the HIV-1 envelope protein. The ROD10 Env also enhanced HIV-1 particle release in the context of HIV-2 chimeric viruses containing the HIV-1 gag-pol, indicating a lack of need for additional HIV-1 products in this process. In addition, we show for the first time that HIV-1 Vpu, as well as ROD10 Env, has the ability to enhance simian immunodeficiency virus (SIV) particle release. The effects of Vpu and ROD10 Env on SIV particle release were indistinguishable and were observed in the context of full-length SIVmac239 and simian-human immunodeficiency virus chimeras. These results further demonstrate that ROD10 Env can functionally complement Vpu with respect to virus release. In contrast, we found no evidence of a destabilizing activity of ROD10 Env on the CD4 molecule. HIV-1 and HIV-2 thus appear to have evolved genetically distinct but functionally similar strategies to resolve the common problem of efficient release of progeny virus from infected cells.
Full Text
The Full Text of this article is available as a PDF (959.7 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Adachi A., Gendelman H. E., Koenig S., Folks T., Willey R., Rabson A., Martin M. A. Production of acquired immunodeficiency syndrome-associated retrovirus in human and nonhuman cells transfected with an infectious molecular clone. J Virol. 1986 Aug;59(2):284–291. doi: 10.1128/jvi.59.2.284-291.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Agy M. B., Frumkin L. R., Corey L., Coombs R. W., Wolinsky S. M., Koehler J., Morton W. R., Katze M. G. Infection of Macaca nemestrina by human immunodeficiency virus type-1. Science. 1992 Jul 3;257(5066):103–106. doi: 10.1126/science.1621083. [DOI] [PubMed] [Google Scholar]
- Bour S., Boulerice F., Wainberg M. A. Inhibition of gp160 and CD4 maturation in U937 cells after both defective and productive infections by human immunodeficiency virus type 1. J Virol. 1991 Dec;65(12):6387–6396. doi: 10.1128/jvi.65.12.6387-6396.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bour S., Schubert U., Peden K., Strebel K. The envelope glycoprotein of human immunodeficiency virus type 2 enhances viral particle release: a Vpu-like factor? J Virol. 1996 Feb;70(2):820–829. doi: 10.1128/jvi.70.2.820-829.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bour S., Schubert U., Strebel K. The human immunodeficiency virus type 1 Vpu protein specifically binds to the cytoplasmic domain of CD4: implications for the mechanism of degradation. J Virol. 1995 Mar;69(3):1510–1520. doi: 10.1128/jvi.69.3.1510-1520.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chen M. Y., Maldarelli F., Karczewski M. K., Willey R. L., Strebel K. Human immunodeficiency virus type 1 Vpu protein induces degradation of CD4 in vitro: the cytoplasmic domain of CD4 contributes to Vpu sensitivity. J Virol. 1993 Jul;67(7):3877–3884. doi: 10.1128/jvi.67.7.3877-3884.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cohen E. A., Terwilliger E. F., Sodroski J. G., Haseltine W. A. Identification of a protein encoded by the vpu gene of HIV-1. Nature. 1988 Aug 11;334(6182):532–534. doi: 10.1038/334532a0. [DOI] [PubMed] [Google Scholar]
- Cucchiarini M., Cagnon L., Giordanengo V., Doglio A., Lefebvre J. C. Induction by human immunodeficiency viruses types 1 and 2 of degradation of CD4 but not of a CD4 mutant unable to bind viral envelope glycoproteins. J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Apr 15;8(5):427–436. [PubMed] [Google Scholar]
- Deen K. C., McDougal J. S., Inacker R., Folena-Wasserman G., Arthos J., Rosenberg J., Maddon P. J., Axel R., Sweet R. W. A soluble form of CD4 (T4) protein inhibits AIDS virus infection. Nature. 1988 Jan 7;331(6151):82–84. doi: 10.1038/331082a0. [DOI] [PubMed] [Google Scholar]
- Friborg J., Ladha A., Göttlinger H., Haseltine W. A., Cohen E. A. Functional analysis of the phosphorylation sites on the human immunodeficiency virus type 1 Vpu protein. J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Jan 1;8(1):10–22. [PubMed] [Google Scholar]
- Friborg J., Yao X. J., Boisvert F., Garzon S., Cohen E. A. Mutational analysis of the HIV-1 Vpu protein. Leukemia. 1994 Apr;8 (Suppl 1):S156–S162. [PubMed] [Google Scholar]
- Geraghty R. J., Panganiban A. T. Human immunodeficiency virus type 1 Vpu has a CD4- and an envelope glycoprotein-independent function. J Virol. 1993 Jul;67(7):4190–4194. doi: 10.1128/jvi.67.7.4190-4194.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Göttlinger H. G., Dorfman T., Cohen E. A., Haseltine W. A. Vpu protein of human immunodeficiency virus type 1 enhances the release of capsids produced by gag gene constructs of widely divergent retroviruses. Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7381–7385. doi: 10.1073/pnas.90.15.7381. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Huet T., Cheynier R., Meyerhans A., Roelants G., Wain-Hobson S. Genetic organization of a chimpanzee lentivirus related to HIV-1. Nature. 1990 May 24;345(6273):356–359. doi: 10.1038/345356a0. [DOI] [PubMed] [Google Scholar]
- Ivey-Hoyle M., Culp J. S., Chaikin M. A., Hellmig B. D., Matthews T. J., Sweet R. W., Rosenberg M. Envelope glycoproteins from biologically diverse isolates of immunodeficiency viruses have widely different affinities for CD4. Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):512–516. doi: 10.1073/pnas.88.2.512. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jabbar M. A., Nayak D. P. Intracellular interaction of human immunodeficiency virus type 1 (ARV-2) envelope glycoprotein gp160 with CD4 blocks the movement and maturation of CD4 to the plasma membrane. J Virol. 1990 Dec;64(12):6297–6304. doi: 10.1128/jvi.64.12.6297-6304.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Klimkait T., Strebel K., Hoggan M. D., Martin M. A., Orenstein J. M. The human immunodeficiency virus type 1-specific protein vpu is required for efficient virus maturation and release. J Virol. 1990 Feb;64(2):621–629. doi: 10.1128/jvi.64.2.621-629.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kong L. I., Lee S. W., Kappes J. C., Parkin J. S., Decker D., Hoxie J. A., Hahn B. H., Shaw G. M. West African HIV-2-related human retrovirus with attenuated cytopathicity. Science. 1988 Jun 10;240(4858):1525–1529. doi: 10.1126/science.3375832. [DOI] [PubMed] [Google Scholar]
- Kumar P., Hui H. X., Kappes J. C., Haggarty B. S., Hoxie J. A., Arya S. K., Shaw G. M., Hahn B. H. Molecular characterization of an attenuated human immunodeficiency virus type 2 isolate. J Virol. 1990 Feb;64(2):890–901. doi: 10.1128/jvi.64.2.890-901.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lenburg M. E., Landau N. R. Vpu-induced degradation of CD4: requirement for specific amino acid residues in the cytoplasmic domain of CD4. J Virol. 1993 Dec;67(12):7238–7245. doi: 10.1128/jvi.67.12.7238-7245.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Li J. T., Halloran M., Lord C. I., Watson A., Ranchalis J., Fung M., Letvin N. L., Sodroski J. G. Persistent infection of macaques with simian-human immunodeficiency viruses. J Virol. 1995 Nov;69(11):7061–7067. doi: 10.1128/jvi.69.11.7061-7067.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Maldarelli F., Chen M. Y., Willey R. L., Strebel K. Human immunodeficiency virus type 1 Vpu protein is an oligomeric type I integral membrane protein. J Virol. 1993 Aug;67(8):5056–5061. doi: 10.1128/jvi.67.8.5056-5061.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marcus-Sekura C. J., Woerner A. M., Zweig M., Court D. L., Levin J. G., Klutch M. Expression of HIV-1 integrase in E. coli: immunological analysis of the recombinant protein. AIDS Res Hum Retroviruses. 1990 Dec;6(12):1399–1408. doi: 10.1089/aid.1990.6.1399. [DOI] [PubMed] [Google Scholar]
- Matsuda Z., Chou M. J., Matsuda M., Huang J. H., Chen Y. M., Redfield R., Mayer K., Essex M., Lee T. H. Human immunodeficiency virus type 1 has an additional coding sequence in the central region of the genome. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6968–6972. doi: 10.1073/pnas.85.18.6968. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mulligan M. J., Ritter G. D., Jr, Chaikin M. A., Yamshchikov G. V., Kumar P., Hahn B. H., Sweet R. W., Compans R. W. Human immunodeficiency virus type 2 envelope glycoprotein: differential CD4 interactions of soluble gp120 versus the assembled envelope complex. Virology. 1992 Mar;187(1):233–241. doi: 10.1016/0042-6822(92)90311-c. [DOI] [PubMed] [Google Scholar]
- Mulligan M. J., Yamshchikov G. V., Ritter G. D., Jr, Gao F., Jin M. J., Nail C. D., Spies C. P., Hahn B. H., Compans R. W. Cytoplasmic domain truncation enhances fusion activity by the exterior glycoprotein complex of human immunodeficiency virus type 2 in selected cell types. J Virol. 1992 Jun;66(6):3971–3975. doi: 10.1128/jvi.66.6.3971-3975.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Naidu Y. M., Kestler H. W., 3rd, Li Y., Butler C. V., Silva D. P., Schmidt D. K., Troup C. D., Sehgal P. K., Sonigo P., Daniel M. D. Characterization of infectious molecular clones of simian immunodeficiency virus (SIVmac) and human immunodeficiency virus type 2: persistent infection of rhesus monkeys with molecularly cloned SIVmac. J Virol. 1988 Dec;62(12):4691–4696. doi: 10.1128/jvi.62.12.4691-4696.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rey M. A., Krust B., Laurent A. G., Montagnier L., Hovanessian A. G. Characterization of human immunodeficiency virus type 2 envelope glycoproteins: dimerization of the glycoprotein precursor during processing. J Virol. 1989 Feb;63(2):647–658. doi: 10.1128/jvi.63.2.647-658.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ritter G. D., Jr, Yamshchikov G., Cohen S. J., Mulligan M. J. Human immunodeficiency virus type 2 glycoprotein enhancement of particle budding: role of the cytoplasmic domain. J Virol. 1996 Apr;70(4):2669–2673. doi: 10.1128/jvi.70.4.2669-2673.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ryan-Graham M. A., Peden K. W. Both virus and host components are important for the manifestation of a Nef- phenotype in HIV-1 and HIV-2. Virology. 1995 Oct 20;213(1):158–168. doi: 10.1006/viro.1995.1556. [DOI] [PubMed] [Google Scholar]
- Schubert U., Bour S., Ferrer-Montiel A. V., Montal M., Maldarell F., Strebel K. The two biological activities of human immunodeficiency virus type 1 Vpu protein involve two separable structural domains. J Virol. 1996 Feb;70(2):809–819. doi: 10.1128/jvi.70.2.809-819.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schubert U., Clouse K. A., Strebel K. Augmentation of virus secretion by the human immunodeficiency virus type 1 Vpu protein is cell type independent and occurs in cultured human primary macrophages and lymphocytes. J Virol. 1995 Dec;69(12):7699–7711. doi: 10.1128/jvi.69.12.7699-7711.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schubert U., Henklein P., Boldyreff B., Wingender E., Strebel K., Porstmann T. The human immunodeficiency virus type 1 encoded Vpu protein is phosphorylated by casein kinase-2 (CK-2) at positions Ser52 and Ser56 within a predicted alpha-helix-turn-alpha-helix-motif. J Mol Biol. 1994 Feb 11;236(1):16–25. doi: 10.1006/jmbi.1994.1114. [DOI] [PubMed] [Google Scholar]
- Schubert U., Schneider T., Henklein P., Hoffmann K., Berthold E., Hauser H., Pauli G., Porstmann T. Human-immunodeficiency-virus-type-1-encoded Vpu protein is phosphorylated by casein kinase II. Eur J Biochem. 1992 Mar 1;204(2):875–883. doi: 10.1111/j.1432-1033.1992.tb16707.x. [DOI] [PubMed] [Google Scholar]
- Schubert U., Strebel K. Differential activities of the human immunodeficiency virus type 1-encoded Vpu protein are regulated by phosphorylation and occur in different cellular compartments. J Virol. 1994 Apr;68(4):2260–2271. doi: 10.1128/jvi.68.4.2260-2271.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schwartz S., Felber B. K., Fenyö E. M., Pavlakis G. N. Env and Vpu proteins of human immunodeficiency virus type 1 are produced from multiple bicistronic mRNAs. J Virol. 1990 Nov;64(11):5448–5456. doi: 10.1128/jvi.64.11.5448-5456.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shibata R., Hoggan M. D., Broscius C., Englund G., Theodore T. S., Buckler-White A., Arthur L. O., Israel Z., Schultz A., Lane H. C. Isolation and characterization of a syncytium-inducing, macrophage/T-cell line-tropic human immunodeficiency virus type 1 isolate that readily infects chimpanzee cells in vitro and in vivo. J Virol. 1995 Jul;69(7):4453–4462. doi: 10.1128/jvi.69.7.4453-4462.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shibata R., Kawamura M., Sakai H., Hayami M., Ishimoto A., Adachi A. Generation of a chimeric human and simian immunodeficiency virus infectious to monkey peripheral blood mononuclear cells. J Virol. 1991 Jul;65(7):3514–3520. doi: 10.1128/jvi.65.7.3514-3520.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Strebel K., Klimkait T., Maldarelli F., Martin M. A. Molecular and biochemical analyses of human immunodeficiency virus type 1 vpu protein. J Virol. 1989 Sep;63(9):3784–3791. doi: 10.1128/jvi.63.9.3784-3791.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Strebel K., Klimkait T., Martin M. A. A novel gene of HIV-1, vpu, and its 16-kilodalton product. Science. 1988 Sep 2;241(4870):1221–1223. doi: 10.1126/science.3261888. [DOI] [PubMed] [Google Scholar]
- Terwilliger E. F., Cohen E. A., Lu Y. C., Sodroski J. G., Haseltine W. A. Functional role of human immunodeficiency virus type 1 vpu. Proc Natl Acad Sci U S A. 1989 Jul;86(13):5163–5167. doi: 10.1073/pnas.86.13.5163. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vincent M. J., Raja N. U., Jabbar M. A. Human immunodeficiency virus type 1 Vpu protein induces degradation of chimeric envelope glycoproteins bearing the cytoplasmic and anchor domains of CD4: role of the cytoplasmic domain in Vpu-induced degradation in the endoplasmic reticulum. J Virol. 1993 Sep;67(9):5538–5549. doi: 10.1128/jvi.67.9.5538-5549.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Willey R. L., Maldarelli F., Martin M. A., Strebel K. Human immunodeficiency virus type 1 Vpu protein induces rapid degradation of CD4. J Virol. 1992 Dec;66(12):7193–7200. doi: 10.1128/jvi.66.12.7193-7200.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Willey R. L., Maldarelli F., Martin M. A., Strebel K. Human immunodeficiency virus type 1 Vpu protein regulates the formation of intracellular gp160-CD4 complexes. J Virol. 1992 Jan;66(1):226–234. doi: 10.1128/jvi.66.1.226-234.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yao X. J., Garzon S., Boisvert F., Haseltine W. A., Cohen E. A. The effect of vpu on HIV-1-induced syncytia formation. J Acquir Immune Defic Syndr. 1993 Feb;6(2):135–141. [PubMed] [Google Scholar]
- Yao X. J., Göttlinger H., Haseltine W. A., Cohen E. A. Envelope glycoprotein and CD4 independence of vpu-facilitated human immunodeficiency virus type 1 capsid export. J Virol. 1992 Aug;66(8):5119–5126. doi: 10.1128/jvi.66.8.5119-5126.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]