p6Gag is required for particle production from full-length human immunodeficiency virus type 1 molecular clones expressing protease (original) (raw)

Abstract

The human immunodeficiency virus type 1 (HIV-1) Gag protein precursor, Pr55Gag, contains at its C-terminal end a proline-rich, 6-kDa domain designated p6. Two functions have been proposed for p6: incorporation of the HIV-1 accessory protein Vpr into virus particles and virus particle production. To characterize the role of p6 in the HIV-1 life cycle and to map functional domains within p6, we introduced a number of nonsense and single and multiple amino acid substitution mutations into p6. Following the introduction of the mutations into the full-length HIV-1 molecular clone pNL4-3, the effects on Gag protein expression and processing, virus particle production, and virus infectivity were analyzed. The production of mutant virus particles was also examined by transmission electron microscopy. The results indicate that (i) p6 is required for efficient virus particle production from a full-length HIV-1 molecular clone; (ii) a Pro-Thr-Ala-Pro sequence, located between residues 7 and 10 of p6, is critical for virus particle production; (iii) mutations outside the Pro-Thr-Ala-Pro motif have little or no effect on virus assembly and release; (iv) the p6 defect is manifested at a late stage in the budding process; and (v) mutations in p6 that severely reduce virion production in HeLa cells also block or significantly delay the establishment of a productive infection in the CEM (12D-7) T-cell line. We further demonstrate that mutational inactivation of the viral protease reverses the p6 defect, suggesting a functional linkage between p6 and the proteolytic processing of the Gag precursor protein during the budding of progeny virions.

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Selected References

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  1. 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]
  2. Bennett R. P., Nelle T. D., Wills J. W. Functional chimeras of the Rous sarcoma virus and human immunodeficiency virus gag proteins. J Virol. 1993 Nov;67(11):6487–6498. doi: 10.1128/jvi.67.11.6487-6498.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bowles N., Bonnet D., Mulhauser F., Spahr P. F. Site-directed mutagenesis of the P2 region of the Rous sarcoma virus gag gene: effects on Gag polyprotein processing. Virology. 1994 Aug 15;203(1):20–28. doi: 10.1006/viro.1994.1450. [DOI] [PubMed] [Google Scholar]
  4. Bryant M., Ratner L. Myristoylation-dependent replication and assembly of human immunodeficiency virus 1. Proc Natl Acad Sci U S A. 1990 Jan;87(2):523–527. doi: 10.1073/pnas.87.2.523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chazal N., Carrière C., Gay B., Boulanger P. Phenotypic characterization of insertion mutants of the human immunodeficiency virus type 1 Gag precursor expressed in recombinant baculovirus-infected cells. J Virol. 1994 Jan;68(1):111–122. doi: 10.1128/jvi.68.1.111-122.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cohen G. B., Ren R., Baltimore D. Modular binding domains in signal transduction proteins. Cell. 1995 Jan 27;80(2):237–248. doi: 10.1016/0092-8674(95)90406-9. [DOI] [PubMed] [Google Scholar]
  7. Copeland N. G., Jenkins N. A., Nexø B., Schultz A. M., Rein A., Mikkelsen T., Jørgensen P. Poorly expressed endogenous ecotropic provirus of DBA/2 mice encodes a mutant Pr65gag protein that is not myristylated. J Virol. 1988 Feb;62(2):479–487. doi: 10.1128/jvi.62.2.479-487.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. DeLuca-Flaherty C., McKay D. B., Parham P., Hill B. L. Uncoating protein (hsc70) binds a conformationally labile domain of clathrin light chain LCa to stimulate ATP hydrolysis. Cell. 1990 Sep 7;62(5):875–887. doi: 10.1016/0092-8674(90)90263-e. [DOI] [PubMed] [Google Scholar]
  9. Dorfman T., Bukovsky A., Ohagen A., Höglund S., Göttlinger H. G. Functional domains of the capsid protein of human immunodeficiency virus type 1. J Virol. 1994 Dec;68(12):8180–8187. doi: 10.1128/jvi.68.12.8180-8187.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dorfman T., Luban J., Goff S. P., Haseltine W. A., Göttlinger H. G. Mapping of functionally important residues of a cysteine-histidine box in the human immunodeficiency virus type 1 nucleocapsid protein. J Virol. 1993 Oct;67(10):6159–6169. doi: 10.1128/jvi.67.10.6159-6169.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dorfman T., Mammano F., Haseltine W. A., Göttlinger H. G. Role of the matrix protein in the virion association of the human immunodeficiency virus type 1 envelope glycoprotein. J Virol. 1994 Mar;68(3):1689–1696. doi: 10.1128/jvi.68.3.1689-1696.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dupraz P., Oertle S., Meric C., Damay P., Spahr P. F. Point mutations in the proximal Cys-His box of Rous sarcoma virus nucleocapsid protein. J Virol. 1990 Oct;64(10):4978–4987. doi: 10.1128/jvi.64.10.4978-4987.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Freed E. O., Martin M. A. Evidence for a functional interaction between the V1/V2 and C4 domains of human immunodeficiency virus type 1 envelope glycoprotein gp120. J Virol. 1994 Apr;68(4):2503–2512. doi: 10.1128/jvi.68.4.2503-2512.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Freed E. O., Martin M. A. Virion incorporation of envelope glycoproteins with long but not short cytoplasmic tails is blocked by specific, single amino acid substitutions in the human immunodeficiency virus type 1 matrix. J Virol. 1995 Mar;69(3):1984–1989. doi: 10.1128/jvi.69.3.1984-1989.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Freed E. O., Orenstein J. M., Buckler-White A. J., Martin M. A. Single amino acid changes in the human immunodeficiency virus type 1 matrix protein block virus particle production. J Virol. 1994 Aug;68(8):5311–5320. doi: 10.1128/jvi.68.8.5311-5320.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. Goff S. P., Lobel L. I. Mutants of murine leukemia viruses and retroviral replication. Biochim Biophys Acta. 1987 Jul 8;907(2):93–123. doi: 10.1016/0304-419x(87)90001-1. [DOI] [PubMed] [Google Scholar]
  18. Gorelick R. J., Henderson L. E., Hanser J. P., Rein A. Point mutants of Moloney murine leukemia virus that fail to package viral RNA: evidence for specific RNA recognition by a "zinc finger-like" protein sequence. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8420–8424. doi: 10.1073/pnas.85.22.8420. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. 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]
  21. Hockley D. J., Nermut M. V., Grief C., Jowett J. B., Jones I. M. Comparative morphology of Gag protein structures produced by mutants of the gag gene of human immunodeficiency virus type 1. J Gen Virol. 1994 Nov;75(Pt 11):2985–2997. doi: 10.1099/0022-1317-75-11-2985. [DOI] [PubMed] [Google Scholar]
  22. Hoshikawa N., Kojima A., Yasuda A., Takayashiki E., Masuko S., Chiba J., Sata T., Kurata T. Role of the gag and pol genes of human immunodeficiency virus in the morphogenesis and maturation of retrovirus-like particles expressed by recombinant vaccinia virus: an ultrastructural study. J Gen Virol. 1991 Oct;72(Pt 10):2509–2517. doi: 10.1099/0022-1317-72-10-2509. [DOI] [PubMed] [Google Scholar]
  23. Jowett J. B., Hockley D. J., Nermut M. V., Jones I. M. Distinct signals in human immunodeficiency virus type 1 Pr55 necessary for RNA binding and particle formation. J Gen Virol. 1992 Dec;73(Pt 12):3079–3086. doi: 10.1099/0022-1317-73-12-3079. [DOI] [PubMed] [Google Scholar]
  24. Jørgensen E. C., Kjeldgaard N. O., Pedersen F. S., Jørgensen P. A nucleotide substitution in the gag N terminus of the endogenous ecotropic DBA/2 virus prevents Pr65gag myristylation and virus replication. J Virol. 1988 Sep;62(9):3217–3223. doi: 10.1128/jvi.62.9.3217-3223.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Jørgensen E. C., Pedersen F. S., Jørgensen P. Matrix protein of Akv murine leukemia virus: genetic mapping of regions essential for particle formation. J Virol. 1992 Jul;66(7):4479–4487. doi: 10.1128/jvi.66.7.4479-4487.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Kaplan A. H., Manchester M., Swanstrom R. The activity of the protease of human immunodeficiency virus type 1 is initiated at the membrane of infected cells before the release of viral proteins and is required for release to occur with maximum efficiency. J Virol. 1994 Oct;68(10):6782–6786. doi: 10.1128/jvi.68.10.6782-6786.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Kaplan A. H., Zack J. A., Knigge M., Paul D. A., Kempf D. J., Norbeck D. W., Swanstrom R. Partial inhibition of the human immunodeficiency virus type 1 protease results in aberrant virus assembly and the formation of noninfectious particles. J Virol. 1993 Jul;67(7):4050–4055. doi: 10.1128/jvi.67.7.4050-4055.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Karacostas V., Wolffe E. J., Nagashima K., Gonda M. A., Moss B. Overexpression of the HIV-1 gag-pol polyprotein results in intracellular activation of HIV-1 protease and inhibition of assembly and budding of virus-like particles. Virology. 1993 Apr;193(2):661–671. doi: 10.1006/viro.1993.1174. [DOI] [PubMed] [Google Scholar]
  29. Katoh I., Yoshinaka Y., Rein A., Shibuya M., Odaka T., Oroszlan S. Murine leukemia virus maturation: protease region required for conversion from "immature" to "mature" core form and for virus infectivity. Virology. 1985 Sep;145(2):280–292. doi: 10.1016/0042-6822(85)90161-8. [DOI] [PubMed] [Google Scholar]
  30. Kondo E., Mammano F., Cohen E. A., Göttlinger H. G. The p6gag domain of human immunodeficiency virus type 1 is sufficient for the incorporation of Vpr into heterologous viral particles. J Virol. 1995 May;69(5):2759–2764. doi: 10.1128/jvi.69.5.2759-2764.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Kräusslich H. G., Fäcke M., Heuser A. M., Konvalinka J., Zentgraf H. The spacer peptide between human immunodeficiency virus capsid and nucleocapsid proteins is essential for ordered assembly and viral infectivity. J Virol. 1995 Jun;69(6):3407–3419. doi: 10.1128/jvi.69.6.3407-3419.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. 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]
  33. Leis J., Jentoft J. Characteristics and regulation of interaction of avian retrovirus pp12 protein with viral RNA. J Virol. 1983 Nov;48(2):361–369. doi: 10.1128/jvi.48.2.361-369.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Lobel L. I., Goff S. P. Construction of mutants of Moloney murine leukemia virus by suppressor-linker insertional mutagenesis: positions of viable insertion mutations. Proc Natl Acad Sci U S A. 1984 Jul;81(13):4149–4153. doi: 10.1073/pnas.81.13.4149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Loeb D. D., Swanstrom R., Everitt L., Manchester M., Stamper S. E., Hutchison C. A., 3rd Complete mutagenesis of the HIV-1 protease. Nature. 1989 Aug 3;340(6232):397–400. doi: 10.1038/340397a0. [DOI] [PubMed] [Google Scholar]
  36. Lu Y. L., Spearman P., Ratner L. Human immunodeficiency virus type 1 viral protein R localization in infected cells and virions. J Virol. 1993 Nov;67(11):6542–6550. doi: 10.1128/jvi.67.11.6542-6550.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Luo L., Li Y., Dales S., Kang C. Y. Mapping of functional domains for HIV-2 gag assembly into virus-like particles. Virology. 1994 Dec;205(2):496–502. doi: 10.1006/viro.1994.1670. [DOI] [PubMed] [Google Scholar]
  38. Luukkonen B. G., Fenyö E. M., Schwartz S. Overexpression of human immunodeficiency virus type 1 protease increases intracellular cleavage of Gag and reduces virus infectivity. Virology. 1995 Feb 1;206(2):854–865. doi: 10.1006/viro.1995.1008. [DOI] [PubMed] [Google Scholar]
  39. Mammano F., Ohagen A., Höglund S., Göttlinger H. G. Role of the major homology region of human immunodeficiency virus type 1 in virion morphogenesis. J Virol. 1994 Aug;68(8):4927–4936. doi: 10.1128/jvi.68.8.4927-4936.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. McQuade T. J., Tomasselli A. G., Liu L., Karacostas V., Moss B., Sawyer T. K., Heinrikson R. L., Tarpley W. G. A synthetic HIV-1 protease inhibitor with antiviral activity arrests HIV-like particle maturation. Science. 1990 Jan 26;247(4941):454–456. doi: 10.1126/science.2405486. [DOI] [PubMed] [Google Scholar]
  41. Mergener K., Fäcke M., Welker R., Brinkmann V., Gelderblom H. R., Kräusslich H. G. Analysis of HIV particle formation using transient expression of subviral constructs in mammalian cells. Virology. 1992 Jan;186(1):25–39. doi: 10.1016/0042-6822(92)90058-w. [DOI] [PubMed] [Google Scholar]
  42. 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]
  43. Méric C., Spahr P. F. Rous sarcoma virus nucleic acid-binding protein p12 is necessary for viral 70S RNA dimer formation and packaging. J Virol. 1986 Nov;60(2):450–459. doi: 10.1128/jvi.60.2.450-459.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Ottmann M., Gabus C., Darlix J. L. The central globular domain of the nucleocapsid protein of human immunodeficiency virus type 1 is critical for virion structure and infectivity. J Virol. 1995 Mar;69(3):1778–1784. doi: 10.1128/jvi.69.3.1778-1784.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Pal R., Reitz M. S., Jr, Tschachler E., Gallo R. C., Sarngadharan M. G., Veronese F. D. Myristoylation of gag proteins of HIV-1 plays an important role in virus assembly. AIDS Res Hum Retroviruses. 1990 Jun;6(6):721–730. doi: 10.1089/aid.1990.6.721. [DOI] [PubMed] [Google Scholar]
  46. Paxton W., Connor R. I., Landau N. R. Incorporation of Vpr into human immunodeficiency virus type 1 virions: requirement for the p6 region of gag and mutational analysis. J Virol. 1993 Dec;67(12):7229–7237. doi: 10.1128/jvi.67.12.7229-7237.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Peng C., Ho B. K., Chang T. W., Chang N. T. Role of human immunodeficiency virus type 1-specific protease in core protein maturation and viral infectivity. J Virol. 1989 Jun;63(6):2550–2556. doi: 10.1128/jvi.63.6.2550-2556.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Pettit S. C., Moody M. D., Wehbie R. S., Kaplan A. H., Nantermet P. V., Klein C. A., Swanstrom R. The p2 domain of human immunodeficiency virus type 1 Gag regulates sequential proteolytic processing and is required to produce fully infectious virions. J Virol. 1994 Dec;68(12):8017–8027. doi: 10.1128/jvi.68.12.8017-8027.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Prats A. C., Sarih L., Gabus C., Litvak S., Keith G., Darlix J. L. Small finger protein of avian and murine retroviruses has nucleic acid annealing activity and positions the replication primer tRNA onto genomic RNA. EMBO J. 1988 Jun;7(6):1777–1783. doi: 10.1002/j.1460-2075.1988.tb03008.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Rhee S. S., Hunter E. Amino acid substitutions within the matrix protein of type D retroviruses affect assembly, transport and membrane association of a capsid. EMBO J. 1991 Mar;10(3):535–546. doi: 10.1002/j.1460-2075.1991.tb07980.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Ross E. K., Buckler-White A. J., Rabson A. B., Englund G., Martin M. A. Contribution of NF-kappa B and Sp1 binding motifs to the replicative capacity of human immunodeficiency virus type 1: distinct patterns of viral growth are determined by T-cell types. J Virol. 1991 Aug;65(8):4350–4358. doi: 10.1128/jvi.65.8.4350-4358.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Royer M., Cerutti M., Gay B., Hong S. S., Devauchelle G., Boulanger P. Functional domains of HIV-1 gag-polyprotein expressed in baculovirus-infected cells. Virology. 1991 Sep;184(1):417–422. doi: 10.1016/0042-6822(91)90861-5. [DOI] [PubMed] [Google Scholar]
  53. Schultz A. M., Rein A. Unmyristylated Moloney murine leukemia virus Pr65gag is excluded from virus assembly and maturation events. J Virol. 1989 May;63(5):2370–2373. doi: 10.1128/jvi.63.5.2370-2373.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. 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]
  55. Sommerfelt M. A., Petteway S. R., Jr, Dreyer G. B., Hunter E. Effect of retroviral proteinase inhibitors on Mason-Pfizer monkey virus maturation and transmembrane glycoprotein cleavage. J Virol. 1992 Jul;66(7):4220–4227. doi: 10.1128/jvi.66.7.4220-4227.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Strambio-de-Castillia C., Hunter E. Mutational analysis of the major homology region of Mason-Pfizer monkey virus by use of saturation mutagenesis. J Virol. 1992 Dec;66(12):7021–7032. doi: 10.1128/jvi.66.12.7021-7032.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Stys D., Blaha I., Strop P. Structural and functional studies in vitro on the p6 protein from the HIV-1 gag open reading frame. Biochim Biophys Acta. 1993 Sep 8;1182(2):157–161. doi: 10.1016/0925-4439(93)90137-p. [DOI] [PubMed] [Google Scholar]
  58. Tritch R. J., Cheng Y. E., Yin F. H., Erickson-Viitanen S. Mutagenesis of protease cleavage sites in the human immunodeficiency virus type 1 gag polyprotein. J Virol. 1991 Feb;65(2):922–930. doi: 10.1128/jvi.65.2.922-930.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Wang C. T., Barklis E. Assembly, processing, and infectivity of human immunodeficiency virus type 1 gag mutants. J Virol. 1993 Jul;67(7):4264–4273. doi: 10.1128/jvi.67.7.4264-4273.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Weaver T. A., Panganiban A. T. N myristoylation of the spleen necrosis virus matrix protein is required for correct association of the Gag polyprotein with intracellular membranes and for particle formation. J Virol. 1990 Aug;64(8):3995–4001. doi: 10.1128/jvi.64.8.3995-4001.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Weldon R. A., Jr, Wills J. W. Characterization of a small (25-kilodalton) derivative of the Rous sarcoma virus Gag protein competent for particle release. J Virol. 1993 Sep;67(9):5550–5561. doi: 10.1128/jvi.67.9.5550-5561.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Willey R. L., Bonifacino J. S., Potts B. J., Martin M. A., Klausner R. D. Biosynthesis, cleavage, and degradation of the human immunodeficiency virus 1 envelope glycoprotein gp160. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9580–9584. doi: 10.1073/pnas.85.24.9580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Willey R. L., Klimkait T., Frucht D. M., Bonifacino J. S., Martin M. A. Mutations within the human immunodeficiency virus type 1 gp160 envelope glycoprotein alter its intracellular transport and processing. Virology. 1991 Sep;184(1):319–329. doi: 10.1016/0042-6822(91)90848-6. [DOI] [PubMed] [Google Scholar]
  64. Willey R. L., Smith D. H., Lasky L. A., Theodore T. S., Earl P. L., Moss B., Capon D. J., Martin M. A. In vitro mutagenesis identifies a region within the envelope gene of the human immunodeficiency virus that is critical for infectivity. J Virol. 1988 Jan;62(1):139–147. doi: 10.1128/jvi.62.1.139-147.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Wills J. W., Cameron C. E., Wilson C. B., Xiang Y., Bennett R. P., Leis J. An assembly domain of the Rous sarcoma virus Gag protein required late in budding. J Virol. 1994 Oct;68(10):6605–6618. doi: 10.1128/jvi.68.10.6605-6618.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Wills J. W., Craven R. C. Form, function, and use of retroviral gag proteins. AIDS. 1991 Jun;5(6):639–654. doi: 10.1097/00002030-199106000-00002. [DOI] [PubMed] [Google Scholar]
  67. Wills J. W., Craven R. C., Weldon R. A., Jr, Nelle T. D., Erdie C. R. Suppression of retroviral MA deletions by the amino-terminal membrane-binding domain of p60src. J Virol. 1991 Jul;65(7):3804–3812. doi: 10.1128/jvi.65.7.3804-3812.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Witte O. N., Baltimore D. Relationship of retrovirus polyprotein cleavages to virion maturation studied with temperature-sensitive murine leukemia virus mutants. J Virol. 1978 Jun;26(3):750–761. doi: 10.1128/jvi.26.3.750-761.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Wu X., Conway J. A., Kim J., Kappes J. C. Localization of the Vpx packaging signal within the C terminus of the human immunodeficiency virus type 2 Gag precursor protein. J Virol. 1994 Oct;68(10):6161–6169. doi: 10.1128/jvi.68.10.6161-6169.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Yu X., Yuan X., Matsuda Z., Lee T. H., Essex M. The matrix protein of human immunodeficiency virus type 1 is required for incorporation of viral envelope protein into mature virions. J Virol. 1992 Aug;66(8):4966–4971. doi: 10.1128/jvi.66.8.4966-4971.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Yuan X., Yu X., Lee T. H., Essex M. Mutations in the N-terminal region of human immunodeficiency virus type 1 matrix protein block intracellular transport of the Gag precursor. J Virol. 1993 Nov;67(11):6387–6394. doi: 10.1128/jvi.67.11.6387-6394.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. von Poblotzki A., Wagner R., Niedrig M., Wanner G., Wolf H., Modrow S. Identification of a region in the Pr55gag-polyprotein essential for HIV-1 particle formation. Virology. 1993 Apr;193(2):981–985. doi: 10.1006/viro.1993.1210. [DOI] [PubMed] [Google Scholar]