HIV Infection of Macrophages: Implications for Pathogenesis and Cure

doi:10.20411/pai.v2i2.204

. 2017;2(2):179-192.

doi: 10.20411/pai.v2i2.204. Epub 2017 May 24.

HIV Infection of Macrophages: Implications for Pathogenesis and Cure

Kiera L Clayton¹, J Victor Garcia², Janice E Clements^{3

4

5}, Bruce D Walker^{1

6

7}

Affiliations

¹ Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts.
² Division of Infectious Diseases, Center for AIDS Research (CFAR), University of North Carolina at Chapel Hill (UNC), School of Medicine, Chapel Hill, North Carolina.
³ Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
⁴ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
⁵ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
⁶ Howard Hughes Medical Institute, Chevy Chase, Maryland.
⁷ Institute of Medical Engineering and Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts.

PMID: 28752134
PMCID: PMC5526341
DOI: 10.20411/pai.v2i2.204

HIV Infection of Macrophages: Implications for Pathogenesis and Cure

Kiera L Clayton et al. Pathog Immun. 2017.

. 2017;2(2):179-192.

doi: 10.20411/pai.v2i2.204. Epub 2017 May 24.

Authors

Kiera L Clayton¹, J Victor Garcia², Janice E Clements^{3

4

5}, Bruce D Walker^{1

6

7}

Affiliations

¹ Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts.
² Division of Infectious Diseases, Center for AIDS Research (CFAR), University of North Carolina at Chapel Hill (UNC), School of Medicine, Chapel Hill, North Carolina.
³ Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
⁴ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
⁵ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
⁶ Howard Hughes Medical Institute, Chevy Chase, Maryland.
⁷ Institute of Medical Engineering and Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts.

PMID: 28752134
PMCID: PMC5526341
DOI: 10.20411/pai.v2i2.204

Abstract

Although CD4⁺ T cells represent the major reservoir of persistent HIV and SIV infection, accumulating evidence suggests that macrophages also contribute. However, investigations of the role of macrophages are often underrepresented at HIV pathogenesis and cure meetings. This was the impetus for a scientific workshop dedicated to this area of study, held in Cambridge, MA in January 2017. The workshop brought together experts in the fields of HIV/SIV immunology and virology, macrophage biology and immunology, and animal models of HIV/SIV infection to discuss the role of macrophages as a physiologically relevant viral reservoir, and the implications of macrophage infection for HIV pathogenesis and strategies for cure. While still controversial, there is an emerging theory that infected macrophages likely persist in the setting of combination antiretroviral therapy. These macrophages could then drive persistent inflammation and contribute to the viral reservoir, which indicates the importance of addressing macrophages as well as CD4⁺ T cells with future therapeutic strategies.

Keywords: HIV/SIV pathogenesis; animal models of HIV infection; macrophages; replication competent virus; viral reservoir.

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Conflict of interest statement

POTENTIAL CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Figures

**Figure 1.**
**HIV-infected macrophage.** Transmission electron microscopy picture of an HIV-infected macrophage taken by Dr. Mike Mashiba and Dr. Kathy Collins (University of Michigan).

See this image and copyright information in PMC

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References

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[1] Swirski FK, Robbins CS, Nahrendorf M. Development and Function of Arterial and Cardiac Macrophages. Trends Immunol. 2016;37(1):32–40. PubMed PMID: 26748179. Pubmed Central PMCID: PMC4706986. doi: 10.1016/j.it.2015.11.004 - DOI - PMC - PubMed

[2] Swirski FK, Robbins CS, Nahrendorf M. Development and Function of Arterial and Cardiac Macrophages. Trends Immunol. 2016;37(1):32–40. PubMed PMID: 26748179. Pubmed Central PMCID: PMC4706986. doi: 10.1016/j.it.2015.11.004 - DOI - PMC - PubMed

[3] Ensan S, Li A, Besla R, Degousee N, Cosme J, Roufaiel M, Shikatani EA, El-Maklizi M, Williams JW, Robins L, Li C, Lewis B, Yun TJ, Lee JS, Wieghofer P, Khattar R, Farrokhi K, Byrne J, Ouzounian M, Zavitz CC, Levy GA, Bauer CM, Libby P, Husain M, Swirski FK, Cheong C, Prinz M, Hilgendorf I, Randolph GJ, Epelman S, Gramolini AO, Cybulsky MI, Rubin BB, Robbins CS. Self-renewing resident arterial macrophages arise from embryonic CX3CR1(+) precursors and circulating monocytes immediately after birth. Nat Immunol. 2016;17(2):159–68. PubMed PMID: 26642357. doi: 10.1038/ni.3343 - DOI - PubMed

[4] Ensan S, Li A, Besla R, Degousee N, Cosme J, Roufaiel M, Shikatani EA, El-Maklizi M, Williams JW, Robins L, Li C, Lewis B, Yun TJ, Lee JS, Wieghofer P, Khattar R, Farrokhi K, Byrne J, Ouzounian M, Zavitz CC, Levy GA, Bauer CM, Libby P, Husain M, Swirski FK, Cheong C, Prinz M, Hilgendorf I, Randolph GJ, Epelman S, Gramolini AO, Cybulsky MI, Rubin BB, Robbins CS. Self-renewing resident arterial macrophages arise from embryonic CX3CR1(+) precursors and circulating monocytes immediately after birth. Nat Immunol. 2016;17(2):159–68. PubMed PMID: 26642357. doi: 10.1038/ni.3343 - DOI - PubMed

[5] Kuritzkes DR. Why cure, why now? J Med Ethics. 2017;43(2):67–70. PubMed PMID: 27273887. Pubmed Central PMCID: PMC5293855. doi: 10.1136/medethics-2015-103113 - DOI - PMC - PubMed

[6] Kuritzkes DR. Why cure, why now? J Med Ethics. 2017;43(2):67–70. PubMed PMID: 27273887. Pubmed Central PMCID: PMC5293855. doi: 10.1136/medethics-2015-103113 - DOI - PMC - PubMed

[7] Delagreverie HM, Delaugerre C, Lewin SR, Deeks SG, Li JZ. Ongoing Clinical Trials of Human Immunodeficiency Virus Latency-Reversing and Immunomodulatory Agents. Open Forum Infect Dis. 2016;3(4):ofw189 PubMed PMID: 27757411. Pubmed Central PMCID: PMC5066458. doi: 10.1093/ofid/ofw189 - DOI - PMC - PubMed

[8] Delagreverie HM, Delaugerre C, Lewin SR, Deeks SG, Li JZ. Ongoing Clinical Trials of Human Immunodeficiency Virus Latency-Reversing and Immunomodulatory Agents. Open Forum Infect Dis. 2016;3(4):ofw189 PubMed PMID: 27757411. Pubmed Central PMCID: PMC5066458. doi: 10.1093/ofid/ofw189 - DOI - PMC - PubMed

[9] Bar KJ, Sneller MC, Harrison LJ, Justement JS, Overton ET, Petrone ME, Salantes DB, Seamon CA, Scheinfeld B, Kwan RW, Learn GH, Proschan MA, Kreider EF, Blazkova J, Bardsley M, Refsland EW, Messer M, Clarridge KE, Tustin NB, Madden PJ, Oden K, O'Dell SJ, Jarocki B, Shiakolas AR, Tressler RL, Doria-Rose NA, Bailer RT, Ledgerwood JE, Capparelli EV, Lynch RM, Graham BS, Moir S, Koup RA, Mascola JR, Hoxie JA, Fauci AS, Tebas P, Chun TW. Effect of HIV Antibody VRC01 on Viral Rebound after Treatment Interruption. N Engl J Med. 2016;375(21):2037–50. PubMed PMID: 27959728. doi: 10.1056/NEJMoa1608243 - DOI - PMC - PubMed

[10] Bar KJ, Sneller MC, Harrison LJ, Justement JS, Overton ET, Petrone ME, Salantes DB, Seamon CA, Scheinfeld B, Kwan RW, Learn GH, Proschan MA, Kreider EF, Blazkova J, Bardsley M, Refsland EW, Messer M, Clarridge KE, Tustin NB, Madden PJ, Oden K, O'Dell SJ, Jarocki B, Shiakolas AR, Tressler RL, Doria-Rose NA, Bailer RT, Ledgerwood JE, Capparelli EV, Lynch RM, Graham BS, Moir S, Koup RA, Mascola JR, Hoxie JA, Fauci AS, Tebas P, Chun TW. Effect of HIV Antibody VRC01 on Viral Rebound after Treatment Interruption. N Engl J Med. 2016;375(21):2037–50. PubMed PMID: 27959728. doi: 10.1056/NEJMoa1608243 - DOI - PMC - PubMed

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HIV Infection of Macrophages: Implications for Pathogenesis and Cure

Affiliations

HIV Infection of Macrophages: Implications for Pathogenesis and Cure

Authors

Affiliations

Abstract

Conflict of interest statement

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Cited by

References

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Abstract

Conflict of interest statement

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References

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