DOI: 10.1073/pnas.0832269100. Visualizing infection of individual influenza viruses

Visualizing infection of individual influenza viruses

10.1073/pnas.0832269100

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Influenza is a paradigm for understanding viral infections. As an opportunistic pathogen exploiting the cellular endocytic machinery for infection, influenza is also a valuable model system for exploring the cell's constitutive endocytic pathway. We have studied the transport, acidification, and fusion of single influenza viruses in living cells by using real-time fluorescence microscopy and have dissected individual stages of the viral entry pathway. The movement of individual viruses revealed a striking three-stage active transport process that preceded viral fusion with endosomes starting with an actin-dependent movement in the cell periphery, followed by a rapid, dynein-directed translocation to the perinuclear region, and finally an intermittent movement involving both plus- and minus-end-directed microtubule-based motilities in the perinuclear region. Surprisingly, the majority of viruses experience their initial acidification in the perinuclear region immediately following the dynein-directed rapid translocation step. This finding suggests a previously undescribed scenario of the endocytic pathway toward late endosomes: endosome maturation, including initial acidification, largely occurs in the perinuclear region.

Bibliography

Lakadamyali, M., Rust, M. J., Babcock, H. P., & Zhuang, X. (2003). Visualizing infection of individual influenza viruses. Proceedings of the National Academy of Sciences, 100(16), 9280â9285.

Authors 4

Melike Lakadamyali (first)
Michael J. Rust (additional)
Hazen P. Babcock (additional)
Xiaowei Zhuang (additional)

References 33 Referenced 642

10.1083/jcb.91.3.601
Martin, K. & Helenius, A. (1990) J. Virol. 65, 232–244. / J. Virol. (1990)
10.1016/S0065-3527(08)60583-7
10.1016/S0169-409X(98)00002-7
10.1146/annurev.cb.01.110185.000245
10.1038/35096054
10.1034/j.1600-0854.2001.020301.x
10.1016/0968-0004(83)90350-X
10.1073/pnas.87.17.6579
10.1126/science.1064103
10.1083/jcb.144.4.657
10.1083/jcb.200203150
10.1128/JVI.72.12.9645-9655.1998
10.1146/annurev.bi.55.070186.003311
Russ J. C. (1999) in The Image Processing Handbook ed. Whitehead C. (CRC Press Boca Raton FL) pp. 227–303.
Loyter, A., Citovsky, V. & Blumenthal, R. (1988) Methods Biochem. Anal. 33, 129–164.3128721 (10.1002/9780470110546.ch4) / Methods Biochem. Anal. (1988)
10.1016/0005-2736(87)90100-3
10.1128/jvi.65.5.2402-2407.1991
10.1038/342555a0
10.1006/viro.1994.1563
10.1099/0022-1317-42-1-73
10.1128/MMBR.65.4.595-626.2001
10.1038/9048
10.1034/j.1600-0749.2002.01078.x
10.1083/jcb.119.2.367
10.1242/jcs.115.7.1453
10.1146/annurev.cb.05.110189.002321
10.1002/(SICI)1097-0169(1996)34:4<299::AID-CM5>3.0.CO;2-3
10.1083/jcb.108.4.1291
Ichimura, T., Hatae, T. & Ishida, T. (1997) Eur. J. Cell Biol. 74, 41–48.9309389 / Eur. J. Cell Biol. (1997)
10.1002/j.1460-2075.1986.tb04616.x
10.1016/0092-8674(88)90532-6
10.1083/jcb.121.6.1257

Dates

Type	When
Created	22 years ago (Aug. 5, 2003, 1:14 p.m.)
Deposited	1 year, 7 months ago (Jan. 10, 2024, 6:33 a.m.)
Indexed	1 day, 12 hours ago (Aug. 31, 2025, 6:15 a.m.)
Issued	22 years, 1 month ago (July 25, 2003)
Published	22 years, 1 month ago (July 25, 2003)
Published Online	22 years, 1 month ago (July 25, 2003)
Published Print	22 years ago (Aug. 5, 2003)

Funders 0

None

BibTeX

@article{Lakadamyali_2003, title={Visualizing infection of individual influenza viruses}, volume={100}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0832269100}, DOI={10.1073/pnas.0832269100}, number={16}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Lakadamyali, Melike and Rust, Michael J. and Babcock, Hazen P. and Zhuang, Xiaowei}, year={2003}, month=jul, pages={9280–9285} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        8,
        31
      ]
    ],
    "date-time": "2025-08-31T10:15:12Z",
    "timestamp": 1756635312900
  },
  "reference-count": 33,
  "publisher": "Proceedings of the National Academy of Sciences",
  "issue": "16",
  "content-domain": {
    "domain": [
      "www.pnas.org"
    ],
    "crossmark-restriction": true
  },
  "published-print": {
    "date-parts": [
      [
        2003,
        8,
        5
      ]
    ]
  },
  "abstract": "<jats:p>Influenza is a paradigm for understanding viral infections. As an opportunistic pathogen exploiting the cellular endocytic machinery for infection, influenza is also a valuable model system for exploring the cell's constitutive endocytic pathway. We have studied the transport, acidification, and fusion of single influenza viruses in living cells by using real-time fluorescence microscopy and have dissected individual stages of the viral entry pathway. The movement of individual viruses revealed a striking three-stage active transport process that preceded viral fusion with endosomes starting with an actin-dependent movement in the cell periphery, followed by a rapid, dynein-directed translocation to the perinuclear region, and finally an intermittent movement involving both plus- and minus-end-directed microtubule-based motilities in the perinuclear region. Surprisingly, the majority of viruses experience their initial acidification in the perinuclear region immediately following the dynein-directed rapid translocation step. This finding suggests a previously undescribed scenario of the endocytic pathway toward late endosomes: endosome maturation, including initial acidification, largely occurs in the perinuclear region.</jats:p>",
  "DOI": "10.1073/pnas.0832269100",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2003,
        8,
        5
      ]
    ],
    "date-time": "2003-08-05T17:14:48Z",
    "timestamp": 1060103688000
  },
  "page": "9280-9285",
  "update-policy": "http://dx.doi.org/10.1073/pnas.cm10313",
  "source": "Crossref",
  "is-referenced-by-count": 642,
  "title": "Visualizing infection of individual influenza viruses",
  "prefix": "10.1073",
  "volume": "100",
  "author": [
    {
      "given": "Melike",
      "family": "Lakadamyali",
      "sequence": "first",
      "affiliation": [
        {
          "name": "Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138"
        }
      ]
    },
    {
      "given": "Michael J.",
      "family": "Rust",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138"
        }
      ]
    },
    {
      "given": "Hazen P.",
      "family": "Babcock",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138"
        }
      ]
    },
    {
      "given": "Xiaowei",
      "family": "Zhuang",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138"
        }
      ]
    }
  ],
  "member": "341",
  "published-online": {
    "date-parts": [
      [
        2003,
        7,
        25
      ]
    ]
  },
  "reference": [
    {
      "key": "e_1_3_2_1_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1083/jcb.91.3.601"
    },
    {
      "key": "e_1_3_2_2_2",
      "first-page": "232",
      "volume": "65",
      "year": "1990",
      "unstructured": "Martin, K. & Helenius, A. (1990) J. Virol. 65, 232\u2013244.",
      "journal-title": "J. Virol."
    },
    {
      "key": "e_1_3_2_3_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0065-3527(08)60583-7"
    },
    {
      "key": "e_1_3_2_4_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0169-409X(98)00002-7"
    },
    {
      "key": "e_1_3_2_5_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1146/annurev.cb.01.110185.000245"
    },
    {
      "key": "e_1_3_2_6_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/35096054"
    },
    {
      "key": "e_1_3_2_7_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1034/j.1600-0854.2001.020301.x"
    },
    {
      "key": "e_1_3_2_8_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0968-0004(83)90350-X"
    },
    {
      "key": "e_1_3_2_9_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.87.17.6579"
    },
    {
      "key": "e_1_3_2_10_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.1064103"
    },
    {
      "key": "e_1_3_2_11_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1083/jcb.144.4.657"
    },
    {
      "key": "e_1_3_2_12_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1083/jcb.200203150"
    },
    {
      "key": "e_1_3_2_13_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/JVI.72.12.9645-9655.1998"
    },
    {
      "key": "e_1_3_2_14_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1146/annurev.bi.55.070186.003311"
    },
    {
      "key": "e_1_3_2_15_2",
      "unstructured": "Russ J. C. (1999) in The Image Processing Handbook ed. Whitehead C. (CRC Press Boca Raton FL) pp. 227\u2013303."
    },
    {
      "key": "e_1_3_2_16_2",
      "doi-asserted-by": "crossref",
      "first-page": "129",
      "DOI": "10.1002/9780470110546.ch4",
      "volume": "33",
      "year": "1988",
      "unstructured": "Loyter, A., Citovsky, V. & Blumenthal, R. (1988) Methods Biochem. Anal. 33, 129\u2013164.3128721",
      "journal-title": "Methods Biochem. Anal."
    },
    {
      "key": "e_1_3_2_17_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0005-2736(87)90100-3"
    },
    {
      "key": "e_1_3_2_18_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jvi.65.5.2402-2407.1991"
    },
    {
      "key": "e_1_3_2_19_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/342555a0"
    },
    {
      "key": "e_1_3_2_20_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1006/viro.1994.1563"
    },
    {
      "key": "e_1_3_2_21_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1099/0022-1317-42-1-73"
    },
    {
      "key": "e_1_3_2_22_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/MMBR.65.4.595-626.2001"
    },
    {
      "key": "e_1_3_2_23_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/9048"
    },
    {
      "key": "e_1_3_2_24_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1034/j.1600-0749.2002.01078.x"
    },
    {
      "key": "e_1_3_2_25_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1083/jcb.119.2.367"
    },
    {
      "key": "e_1_3_2_26_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1242/jcs.115.7.1453"
    },
    {
      "key": "e_1_3_2_27_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1146/annurev.cb.05.110189.002321"
    },
    {
      "key": "e_1_3_2_28_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/(SICI)1097-0169(1996)34:4<299::AID-CM5>3.0.CO;2-3"
    },
    {
      "key": "e_1_3_2_29_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1083/jcb.108.4.1291"
    },
    {
      "key": "e_1_3_2_30_2",
      "first-page": "41",
      "volume": "74",
      "year": "1997",
      "unstructured": "Ichimura, T., Hatae, T. & Ishida, T. (1997) Eur. J. Cell Biol. 74, 41\u201348.9309389",
      "journal-title": "Eur. J. Cell Biol."
    },
    {
      "key": "e_1_3_2_31_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/j.1460-2075.1986.tb04616.x"
    },
    {
      "key": "e_1_3_2_32_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(88)90532-6"
    },
    {
      "key": "e_1_3_2_33_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1083/jcb.121.6.1257"
    }
  ],
  "container-title": "Proceedings of the National Academy of Sciences",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://pnas.org/doi/pdf/10.1073/pnas.0832269100",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2024,
        1,
        10
      ]
    ],
    "date-time": "2024-01-10T11:33:24Z",
    "timestamp": 1704886404000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://pnas.org/doi/full/10.1073/pnas.0832269100"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2003,
        7,
        25
      ]
    ]
  },
  "references-count": 33,
  "journal-issue": {
    "issue": "16",
    "published-print": {
      "date-parts": [
        [
          2003,
          8,
          5
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1073/pnas.0832269100"
  ],
  "URL": "http://dx.doi.org/10.1073/pnas.0832269100",
  "relation": {
    "has-review": [
      {
        "id-type": "doi",
        "id": "10.3410/f.1014943.195362",
        "asserted-by": "object"
      },
      {
        "id-type": "doi",
        "id": "10.3410/f.1014943.195409",
        "asserted-by": "object"
      }
    ]
  },
  "ISSN": [
    "0027-8424",
    "1091-6490"
  ],
  "subject": [],
  "container-title-short": "Proc. Natl. Acad. Sci. U.S.A.",
  "published": {
    "date-parts": [
      [
        2003,
        7,
        25
      ]
    ]
  },
  "assertion": [
    {
      "value": "2003-04-03",
      "order": 0,
      "name": "received",
      "label": "Received",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "2003-07-25",
      "order": 2,
      "name": "published",
      "label": "Published",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    }
  ]
}