DOI: 10.1128/jvi.78.10.5500-5506.2004. Human Immunodeficiency Virus Type 1 Envelope Glycoproteins That Lack Cytoplasmic Domain Cysteines: Impact on Association with Membrane Lipid Rafts and Incorporation onto Budding Virus Particles

Human Immunodeficiency Virus Type 1 Envelope Glycoproteins That Lack Cytoplasmic Domain Cysteines: Impact on Association with Membrane Lipid Rafts and Incorporation onto Budding Virus Particles

10.1128/jvi.78.10.5500-5506.2004

Crossref journal-article

American Society for Microbiology

Journal of Virology (235)

Abstract

ABSTRACTThe human immunodeficiency virus type 1 (HIV-1) envelope comprises a surface gp120 and a transmembrane gp41. The cytoplasmic domain of gp41 contains cysteine residues (C764 and C837) which are targets for palmitoylation and were reported to be required for envelope association with lipid rafts and assembly on budding virions (I. Rousso, M. B. Mixon, B. K. Chen, and P. S. Kim, Proc. Natl. Acad. Sci. USA97:13523-13525, 2000). Several infectious HIV-1 clones contain envelopes that have no gp41 cytoplasmic cysteines. Since no other gp41 amino acid is a target for palmitoylation, these clones imply that palmitoylation is not essential for envelope trafficking and assembly. Here, we show that HIV-1 envelope mutants that lack gp41 cytoplasmic cysteines are excluded from light lipid rafts. Envelopes that contained residues with bulky hydrophobic side chains instead of cysteines retained their association with heavy rafts and were nearly fully functional for incorporation into virions and infectivity. Substitution of cysteines with alanines or serines eliminated raft association and more severely reduced envelope incorporation onto virions and their infectivity. Nevertheless, the A764/A837 mutant envelope retained nearly 40% infectivity compared to the wild type, even though this envelope was excluded from lipid rafts. Our results demonstrate that gp41 cytoplasmic cysteines that are targets for palmitoylation and are required for envelope trafficking to classical lipid rafts are not essential for HIV-1 replication.

Bibliography

Bhattacharya, J., Peters, P. J., & Clapham, P. R. (2004). Human Immunodeficiency Virus Type 1 Envelope Glycoproteins That Lack Cytoplasmic Domain Cysteines: Impact on Association with Membrane Lipid Rafts and Incorporation onto Budding Virus Particles. Journal of Virology, 78(10), 5500â5506.

Authors 3

Jayanta Bhattacharya (first)
Paul J. Peters (additional)
Paul R. Clapham (additional)

References 28 Referenced 78

10.1089/aid.1994.10.371
10.1073/pnas.90.11.5181
Brown, D. 2002. Structure and function of membrane rafts. Int. J. Med. Microbiol.291:433-437. / Int. J. Med. Microbiol. (2002)
10.1128/JVI.75.20.9925-9938.2001
10.1128/jvi.62.10.3779-3788.1988
10.1128/jvi.66.11.6547-6554.1992
10.1128/JVI.77.24.12968-12979.2003
10.1128/JVI.76.1.327-337.2002
10.1128/jvi.67.5.2546-2551.1993
10.1128/JVI.77.6.3634-3646.2003
10.1006/bbrc.2002.6583
10.1093/emboj/cdg095
10.1021/bi034159a
10.1074/jbc.274.6.3910
10.1128/JVI.74.8.3548-3554.2000
10.1074/jbc.M205386200
10.1128/JVI.75.23.11544-11554.2001
10.1073/pnas.241320298
Pincus, S. H., K. Wehrly, and B. Chesebro. 1989. Treatment of HIV tissue culture infection with monoclonal antibody-ricin A chain conjugates. J. Immunol.142:3070-3075. (10.4049/jimmunol.142.9.3070) / J. Immunol. (1989)
10.1016/S0167-4889(99)00075-0
10.1073/pnas.240459697
10.1074/jbc.273.2.1150
10.1006/bbrc.1999.0633
10.1089/aid.1997.13.263
10.1006/viro.1995.1547
10.1073/pnas.92.21.9871
10.1016/S0960-9822(99)80511-9
10.1128/jvi.68.9.5748-5754.1994

Dates

Type	When
Created	21 years, 4 months ago (April 27, 2004, 10:20 p.m.)
Deposited	2 years, 4 months ago (April 28, 2023, 9:43 a.m.)
Indexed	1 month, 3 weeks ago (July 12, 2025, 6:57 p.m.)
Issued	21 years, 3 months ago (May 15, 2004)
Published	21 years, 3 months ago (May 15, 2004)
Published Print	21 years, 3 months ago (May 15, 2004)

Funders 0

None

BibTeX

@article{Bhattacharya_2004, title={Human Immunodeficiency Virus Type 1 Envelope Glycoproteins That Lack Cytoplasmic Domain Cysteines: Impact on Association with Membrane Lipid Rafts and Incorporation onto Budding Virus Particles}, volume={78}, ISSN={1098-5514}, url={http://dx.doi.org/10.1128/jvi.78.10.5500-5506.2004}, DOI={10.1128/jvi.78.10.5500-5506.2004}, number={10}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Bhattacharya, Jayanta and Peters, Paul J. and Clapham, Paul R.}, year={2004}, month=may, pages={5500–5506} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        7,
        12
      ]
    ],
    "date-time": "2025-07-12T22:57:20Z",
    "timestamp": 1752361040047
  },
  "reference-count": 28,
  "publisher": "American Society for Microbiology",
  "issue": "10",
  "license": [
    {
      "start": {
        "date-parts": [
          [
            2004,
            5,
            15
          ]
        ],
        "date-time": "2004-05-15T00:00:00Z",
        "timestamp": 1084579200000
      },
      "content-version": "tdm",
      "delay-in-days": 0,
      "URL": "https://journals.asm.org/non-commercial-tdm-license"
    }
  ],
  "content-domain": {
    "domain": [
      "journals.asm.org"
    ],
    "crossmark-restriction": true
  },
  "published-print": {
    "date-parts": [
      [
        2004,
        5,
        15
      ]
    ]
  },
  "abstract": "<jats:title>ABSTRACT</jats:title><jats:p>The human immunodeficiency virus type 1 (HIV-1) envelope comprises a surface gp120 and a transmembrane gp41. The cytoplasmic domain of gp41 contains cysteine residues (C764 and C837) which are targets for palmitoylation and were reported to be required for envelope association with lipid rafts and assembly on budding virions (I. Rousso, M. B. Mixon, B. K. Chen, and P. S. Kim, Proc. Natl. Acad. Sci. USA<jats:bold>97:</jats:bold>13523-13525, 2000). Several infectious HIV-1 clones contain envelopes that have no gp41 cytoplasmic cysteines. Since no other gp41 amino acid is a target for palmitoylation, these clones imply that palmitoylation is not essential for envelope trafficking and assembly. Here, we show that HIV-1 envelope mutants that lack gp41 cytoplasmic cysteines are excluded from light lipid rafts. Envelopes that contained residues with bulky hydrophobic side chains instead of cysteines retained their association with heavy rafts and were nearly fully functional for incorporation into virions and infectivity. Substitution of cysteines with alanines or serines eliminated raft association and more severely reduced envelope incorporation onto virions and their infectivity. Nevertheless, the A764/A837 mutant envelope retained nearly 40% infectivity compared to the wild type, even though this envelope was excluded from lipid rafts. Our results demonstrate that gp41 cytoplasmic cysteines that are targets for palmitoylation and are required for envelope trafficking to classical lipid rafts are not essential for HIV-1 replication.</jats:p>",
  "DOI": "10.1128/jvi.78.10.5500-5506.2004",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2004,
        4,
        28
      ]
    ],
    "date-time": "2004-04-28T02:20:05Z",
    "timestamp": 1083118805000
  },
  "page": "5500-5506",
  "update-policy": "http://dx.doi.org/10.1128/asmj-crossmark-policy-page",
  "source": "Crossref",
  "is-referenced-by-count": 78,
  "title": "Human Immunodeficiency Virus Type 1 Envelope Glycoproteins That Lack Cytoplasmic Domain Cysteines: Impact on Association with Membrane Lipid Rafts and Incorporation onto Budding Virus Particles",
  "prefix": "10.1128",
  "volume": "78",
  "author": [
    {
      "given": "Jayanta",
      "family": "Bhattacharya",
      "sequence": "first",
      "affiliation": [
        {
          "name": "Program in Molecular Medicine and Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, Massachusetts 01605"
        }
      ]
    },
    {
      "given": "Paul J.",
      "family": "Peters",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Program in Molecular Medicine and Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, Massachusetts 01605"
        }
      ]
    },
    {
      "given": "Paul R.",
      "family": "Clapham",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Program in Molecular Medicine and Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, Massachusetts 01605"
        }
      ]
    }
  ],
  "member": "235",
  "reference": [
    {
      "key": "e_1_3_2_2_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1089/aid.1994.10.371"
    },
    {
      "key": "e_1_3_2_3_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.90.11.5181"
    },
    {
      "key": "e_1_3_2_4_2",
      "first-page": "433",
      "volume": "291",
      "year": "2002",
      "unstructured": "Brown, D. 2002. Structure and function of membrane rafts. Int. J. Med. Microbiol.291:433-437.",
      "journal-title": "Int. J. Med. Microbiol."
    },
    {
      "key": "e_1_3_2_5_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/JVI.75.20.9925-9938.2001"
    },
    {
      "key": "e_1_3_2_6_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jvi.62.10.3779-3788.1988"
    },
    {
      "key": "e_1_3_2_7_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jvi.66.11.6547-6554.1992"
    },
    {
      "key": "e_1_3_2_8_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/JVI.77.24.12968-12979.2003"
    },
    {
      "key": "e_1_3_2_9_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/JVI.76.1.327-337.2002"
    },
    {
      "key": "e_1_3_2_10_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jvi.67.5.2546-2551.1993"
    },
    {
      "key": "e_1_3_2_11_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/JVI.77.6.3634-3646.2003"
    },
    {
      "key": "e_1_3_2_12_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1006/bbrc.2002.6583"
    },
    {
      "key": "e_1_3_2_13_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/emboj/cdg095"
    },
    {
      "key": "e_1_3_2_14_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/bi034159a"
    },
    {
      "key": "e_1_3_2_15_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.274.6.3910"
    },
    {
      "key": "e_1_3_2_16_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/JVI.74.8.3548-3554.2000"
    },
    {
      "key": "e_1_3_2_17_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.M205386200"
    },
    {
      "key": "e_1_3_2_18_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/JVI.75.23.11544-11554.2001"
    },
    {
      "key": "e_1_3_2_19_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.241320298"
    },
    {
      "key": "e_1_3_2_20_2",
      "doi-asserted-by": "crossref",
      "first-page": "3070",
      "DOI": "10.4049/jimmunol.142.9.3070",
      "volume": "142",
      "year": "1989",
      "unstructured": "Pincus, S. H., K. Wehrly, and B. Chesebro. 1989. Treatment of HIV tissue culture infection with monoclonal antibody-ricin A chain conjugates. J. Immunol.142:3070-3075.",
      "journal-title": "J. Immunol."
    },
    {
      "key": "e_1_3_2_21_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0167-4889(99)00075-0"
    },
    {
      "key": "e_1_3_2_22_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.240459697"
    },
    {
      "key": "e_1_3_2_23_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.273.2.1150"
    },
    {
      "key": "e_1_3_2_24_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1006/bbrc.1999.0633"
    },
    {
      "key": "e_1_3_2_25_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1089/aid.1997.13.263"
    },
    {
      "key": "e_1_3_2_26_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1006/viro.1995.1547"
    },
    {
      "key": "e_1_3_2_27_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.92.21.9871"
    },
    {
      "key": "e_1_3_2_28_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0960-9822(99)80511-9"
    },
    {
      "key": "e_1_3_2_29_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jvi.68.9.5748-5754.1994"
    }
  ],
  "container-title": "Journal of Virology",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://journals.asm.org/doi/pdf/10.1128/JVI.78.10.5500-5506.2004",
      "content-type": "application/pdf",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://journals.asm.org/doi/pdf/10.1128/JVI.78.10.5500-5506.2004",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2023,
        4,
        28
      ]
    ],
    "date-time": "2023-04-28T13:43:43Z",
    "timestamp": 1682689423000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://journals.asm.org/doi/10.1128/JVI.78.10.5500-5506.2004"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2004,
        5,
        15
      ]
    ]
  },
  "references-count": 28,
  "journal-issue": {
    "issue": "10",
    "published-print": {
      "date-parts": [
        [
          2004,
          5,
          15
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1128/JVI.78.10.5500-5506.2004"
  ],
  "URL": "http://dx.doi.org/10.1128/JVI.78.10.5500-5506.2004",
  "relation": {},
  "ISSN": [
    "0022-538X",
    "1098-5514"
  ],
  "subject": [],
  "container-title-short": "J Virol",
  "published": {
    "date-parts": [
      [
        2004,
        5,
        15
      ]
    ]
  },
  "assertion": [
    {
      "value": "2003-09-10",
      "order": 0,
      "name": "received",
      "label": "Received",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "2004-01-24",
      "order": 1,
      "name": "accepted",
      "label": "Accepted",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "2004-05-15",
      "order": 2,
      "name": "published",
      "label": "Published",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    }
  ]
}