PET/CT targeted tissue sampling reveals virus specific dIgA can alter the distribution and localization of HIV after rectal exposure

Roslyn A. Taylor; Sixia Xiao; Ann M. Carias; Michael D. McRaven; Divya N. Thakkar; Mariluz Araínga; Edward J. Allen; Kenneth A. Rogers; Sidath C. Kumarapperuma; Siqi Gong; Angela J. Fought; Meegan R. Anderson; Yanique Thomas; Jeffrey R. Schneider; Beth Goins; Peter Fox; Francois J. Villinger; Ruth M. Ruprecht; Thomas J. Hope

doi:10.1371/journal.ppat.1009632

PET/CT targeted tissue sampling reveals virus specific dIgA can alter the distribution and localization of HIV after rectal exposure

Roslyn A. Taylor, Sixia Xiao, Ann M. Carias, Michael D. McRaven, Divya N. Thakkar, Mariluz Araínga, Edward J. Allen, Kenneth A. Rogers, Sidath C. Kumarapperuma, Siqi Gong, Angela J. Fought, Meegan R. Anderson, Yanique Thomas, Jeffrey R. Schneider, Beth Goins, Peter Fox, Francois J. Villinger, Ruth M. Ruprecht, Thomas J. Hope^*

^*Corresponding author for this work

Cell & Developmental Biology

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

Human immunodeficiency virus (HIV) vaccines have not been successful in clinical trials. Dimeric IgA (dIgA) in the form of secretory IgA is the most abundant antibody class in mucosal tissues, making dIgA a prime candidate for potential HIV vaccines. We coupled Positron Emission Tomography (PET) imaging and fluorescent microscopy of 64Cu-labeled, photoactivatable- GFP HIV (PA-GFP-BaL) and fluorescently labeled dIgA to determine how dIgA antibodies influence virus interaction with mucosal barriers and viral penetration in colorectal tissue. Our results show that HIV virions rapidly disseminate throughout the colon two hours after exposure. The presence of dIgA resulted in an increase in virions and penetration depth in the transverse colon. Moreover, virions were found in the mesenteric lymph nodes two hours after viral exposure, and the presence of dIgA led to an increase in virions in mesenteric lymph nodes. Taken together, these technologies enable in vivo and in situ visualization of antibody-virus interactions and detailed investigations of early events in HIV infection.

Original language	English (US)
Article number	e1009632
Journal	PLoS pathogens
Volume	17
Issue number	6
DOIs	https://doi.org/10.1371/journal.ppat.1009632
State	Published - Jun 2021

Funding

This work was supported by the National Institutes of Health grants: NIH P01 AI48240 (TJH, SCK, BG, PF, FV, RMR) and NIH P50 AI150464 (TJH), 1 K01 OD026571-01 (AMC), and K01OD024882-01 (JRS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

ASJC Scopus subject areas

Parasitology
Microbiology
Immunology
Molecular Biology
Genetics
Virology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1371/journal.ppat.1009632

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Taylor, R. A., Xiao, S., Carias, A. M., McRaven, M. D., Thakkar, D. N., Araínga, M., Allen, E. J., Rogers, K. A., Kumarapperuma, S. C., Gong, S., Fought, A. J., Anderson, M. R., Thomas, Y., Schneider, J. R., Goins, B., Fox, P., Villinger, F. J., Ruprecht, R. M., & Hope, T. J. (2021). PET/CT targeted tissue sampling reveals virus specific dIgA can alter the distribution and localization of HIV after rectal exposure. PLoS pathogens, 17(6), Article e1009632. https://doi.org/10.1371/journal.ppat.1009632

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title = "PET/CT targeted tissue sampling reveals virus specific dIgA can alter the distribution and localization of HIV after rectal exposure",

abstract = "Human immunodeficiency virus (HIV) vaccines have not been successful in clinical trials. Dimeric IgA (dIgA) in the form of secretory IgA is the most abundant antibody class in mucosal tissues, making dIgA a prime candidate for potential HIV vaccines. We coupled Positron Emission Tomography (PET) imaging and fluorescent microscopy of 64Cu-labeled, photoactivatable- GFP HIV (PA-GFP-BaL) and fluorescently labeled dIgA to determine how dIgA antibodies influence virus interaction with mucosal barriers and viral penetration in colorectal tissue. Our results show that HIV virions rapidly disseminate throughout the colon two hours after exposure. The presence of dIgA resulted in an increase in virions and penetration depth in the transverse colon. Moreover, virions were found in the mesenteric lymph nodes two hours after viral exposure, and the presence of dIgA led to an increase in virions in mesenteric lymph nodes. Taken together, these technologies enable in vivo and in situ visualization of antibody-virus interactions and detailed investigations of early events in HIV infection.",

author = "Taylor, {Roslyn A.} and Sixia Xiao and Carias, {Ann M.} and McRaven, {Michael D.} and Thakkar, {Divya N.} and Mariluz Ara{\'i}nga and Allen, {Edward J.} and Rogers, {Kenneth A.} and Kumarapperuma, {Sidath C.} and Siqi Gong and Fought, {Angela J.} and Anderson, {Meegan R.} and Yanique Thomas and Schneider, {Jeffrey R.} and Beth Goins and Peter Fox and Villinger, {Francois J.} and Ruprecht, {Ruth M.} and Hope, {Thomas J.}",

note = "Publisher Copyright: {\textcopyright} 2021 Taylor et al.",

year = "2021",

month = jun,

doi = "10.1371/journal.ppat.1009632",

language = "English (US)",

volume = "17",

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Taylor, RA, Xiao, S, Carias, AM, McRaven, MD, Thakkar, DN, Araínga, M, Allen, EJ, Rogers, KA, Kumarapperuma, SC, Gong, S, Fought, AJ, Anderson, MR, Thomas, Y, Schneider, JR, Goins, B, Fox, P, Villinger, FJ, Ruprecht, RM & Hope, TJ 2021, 'PET/CT targeted tissue sampling reveals virus specific dIgA can alter the distribution and localization of HIV after rectal exposure', PLoS pathogens, vol. 17, no. 6, e1009632. https://doi.org/10.1371/journal.ppat.1009632

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T1 - PET/CT targeted tissue sampling reveals virus specific dIgA can alter the distribution and localization of HIV after rectal exposure

AU - Taylor, Roslyn A.

AU - Xiao, Sixia

AU - Carias, Ann M.

AU - McRaven, Michael D.

AU - Thakkar, Divya N.

AU - Araínga, Mariluz

AU - Allen, Edward J.

AU - Rogers, Kenneth A.

AU - Kumarapperuma, Sidath C.

AU - Gong, Siqi

AU - Fought, Angela J.

AU - Anderson, Meegan R.

AU - Thomas, Yanique

AU - Schneider, Jeffrey R.

AU - Goins, Beth

AU - Fox, Peter

AU - Villinger, Francois J.

AU - Ruprecht, Ruth M.

AU - Hope, Thomas J.

PY - 2021/6

Y1 - 2021/6

N2 - Human immunodeficiency virus (HIV) vaccines have not been successful in clinical trials. Dimeric IgA (dIgA) in the form of secretory IgA is the most abundant antibody class in mucosal tissues, making dIgA a prime candidate for potential HIV vaccines. We coupled Positron Emission Tomography (PET) imaging and fluorescent microscopy of 64Cu-labeled, photoactivatable- GFP HIV (PA-GFP-BaL) and fluorescently labeled dIgA to determine how dIgA antibodies influence virus interaction with mucosal barriers and viral penetration in colorectal tissue. Our results show that HIV virions rapidly disseminate throughout the colon two hours after exposure. The presence of dIgA resulted in an increase in virions and penetration depth in the transverse colon. Moreover, virions were found in the mesenteric lymph nodes two hours after viral exposure, and the presence of dIgA led to an increase in virions in mesenteric lymph nodes. Taken together, these technologies enable in vivo and in situ visualization of antibody-virus interactions and detailed investigations of early events in HIV infection.

AB - Human immunodeficiency virus (HIV) vaccines have not been successful in clinical trials. Dimeric IgA (dIgA) in the form of secretory IgA is the most abundant antibody class in mucosal tissues, making dIgA a prime candidate for potential HIV vaccines. We coupled Positron Emission Tomography (PET) imaging and fluorescent microscopy of 64Cu-labeled, photoactivatable- GFP HIV (PA-GFP-BaL) and fluorescently labeled dIgA to determine how dIgA antibodies influence virus interaction with mucosal barriers and viral penetration in colorectal tissue. Our results show that HIV virions rapidly disseminate throughout the colon two hours after exposure. The presence of dIgA resulted in an increase in virions and penetration depth in the transverse colon. Moreover, virions were found in the mesenteric lymph nodes two hours after viral exposure, and the presence of dIgA led to an increase in virions in mesenteric lymph nodes. Taken together, these technologies enable in vivo and in situ visualization of antibody-virus interactions and detailed investigations of early events in HIV infection.

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PET/CT targeted tissue sampling reveals virus specific dIgA can alter the distribution and localization of HIV after rectal exposure

Abstract

Funding

ASJC Scopus subject areas

UN SDGs

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