Electron tomography of HIV-1 infection in gut-associated lymphoid tissue.
Critical aspects of HIV-1 infection occur in mucosal tissues, particularly in the gut, which contains large numbers of HIV-1 target cells that are depleted early in infection. We used electron tomography (ET) to image HIV-1 in gut-associated lymphoid tissue (GALT) of HIV-1-infected humanized mice, t...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS Pathogens |
| Online Access: | http://europepmc.org/articles/PMC3907528?pdf=render |
| _version_ | 1818009837865271296 |
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| author | Mark S Ladinsky Collin Kieffer Gregory Olson Maud Deruaz Vladimir Vrbanac Andrew M Tager Douglas S Kwon Pamela J Bjorkman |
| author_facet | Mark S Ladinsky Collin Kieffer Gregory Olson Maud Deruaz Vladimir Vrbanac Andrew M Tager Douglas S Kwon Pamela J Bjorkman |
| author_sort | Mark S Ladinsky |
| collection | DOAJ |
| description | Critical aspects of HIV-1 infection occur in mucosal tissues, particularly in the gut, which contains large numbers of HIV-1 target cells that are depleted early in infection. We used electron tomography (ET) to image HIV-1 in gut-associated lymphoid tissue (GALT) of HIV-1-infected humanized mice, the first three-dimensional ultrastructural examination of HIV-1 infection in vivo. Human immune cells were successfully engrafted in the mice, and following infection with HIV-1, human T cells were reduced in GALT. Virions were found by ET at all stages of egress, including budding immature virions and free mature and immature viruses. Immuno-electron microscopy verified the virions were HIV-1 and showed CD4 sequestration in the endoplasmic reticulum of infected cells. Observation of HIV-1 in infected GALT tissue revealed that most HIV-1-infected cells, identified by immunolabeling and/or the presence of budding virions, were localized to intestinal crypts with pools of free virions concentrated in spaces between cells. Fewer infected cells were found in mucosal regions and the lamina propria. The preservation quality of reconstructed tissue volumes allowed details of budding virions, including structures interpreted as host-encoded scission machinery, to be resolved. Although HIV-1 virions released from infected cultured cells have been described as exclusively mature, we found pools of both immature and mature free virions within infected tissue. The pools could be classified as containing either mostly mature or mostly immature particles, and analyses of their proximities to the cell of origin supported a model of semi-synchronous waves of virion release. In addition to HIV-1 transmission by pools of free virus, we found evidence of transmission via virological synapses. Three-dimensional EM imaging of an active infection within tissue revealed important differences between cultured cell and tissue infection models and furthered the ultrastructural understanding of HIV-1 transmission within lymphoid tissue. |
| first_indexed | 2024-04-14T05:47:59Z |
| format | Article |
| id | doaj.art-d30436f8b85d4f5a8c67bf3b0ee0904c |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-04-14T05:47:59Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-d30436f8b85d4f5a8c67bf3b0ee0904c2022-12-22T02:09:13ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742014-01-01101e100389910.1371/journal.ppat.1003899Electron tomography of HIV-1 infection in gut-associated lymphoid tissue.Mark S LadinskyCollin KiefferGregory OlsonMaud DeruazVladimir VrbanacAndrew M TagerDouglas S KwonPamela J BjorkmanCritical aspects of HIV-1 infection occur in mucosal tissues, particularly in the gut, which contains large numbers of HIV-1 target cells that are depleted early in infection. We used electron tomography (ET) to image HIV-1 in gut-associated lymphoid tissue (GALT) of HIV-1-infected humanized mice, the first three-dimensional ultrastructural examination of HIV-1 infection in vivo. Human immune cells were successfully engrafted in the mice, and following infection with HIV-1, human T cells were reduced in GALT. Virions were found by ET at all stages of egress, including budding immature virions and free mature and immature viruses. Immuno-electron microscopy verified the virions were HIV-1 and showed CD4 sequestration in the endoplasmic reticulum of infected cells. Observation of HIV-1 in infected GALT tissue revealed that most HIV-1-infected cells, identified by immunolabeling and/or the presence of budding virions, were localized to intestinal crypts with pools of free virions concentrated in spaces between cells. Fewer infected cells were found in mucosal regions and the lamina propria. The preservation quality of reconstructed tissue volumes allowed details of budding virions, including structures interpreted as host-encoded scission machinery, to be resolved. Although HIV-1 virions released from infected cultured cells have been described as exclusively mature, we found pools of both immature and mature free virions within infected tissue. The pools could be classified as containing either mostly mature or mostly immature particles, and analyses of their proximities to the cell of origin supported a model of semi-synchronous waves of virion release. In addition to HIV-1 transmission by pools of free virus, we found evidence of transmission via virological synapses. Three-dimensional EM imaging of an active infection within tissue revealed important differences between cultured cell and tissue infection models and furthered the ultrastructural understanding of HIV-1 transmission within lymphoid tissue.http://europepmc.org/articles/PMC3907528?pdf=render |
| spellingShingle | Mark S Ladinsky Collin Kieffer Gregory Olson Maud Deruaz Vladimir Vrbanac Andrew M Tager Douglas S Kwon Pamela J Bjorkman Electron tomography of HIV-1 infection in gut-associated lymphoid tissue. PLoS Pathogens |
| title | Electron tomography of HIV-1 infection in gut-associated lymphoid tissue. |
| title_full | Electron tomography of HIV-1 infection in gut-associated lymphoid tissue. |
| title_fullStr | Electron tomography of HIV-1 infection in gut-associated lymphoid tissue. |
| title_full_unstemmed | Electron tomography of HIV-1 infection in gut-associated lymphoid tissue. |
| title_short | Electron tomography of HIV-1 infection in gut-associated lymphoid tissue. |
| title_sort | electron tomography of hiv 1 infection in gut associated lymphoid tissue |
| url | http://europepmc.org/articles/PMC3907528?pdf=render |
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