A pilot molecular mechanism study on lacrimal gland as a potential human immunodeficiency virus reservoir

Authors: Liu Ziyang,  Liu Xiaowei,  Ye Junjie,  Han Yang,  Li Taisheng,  Huo Zhen

DOI: 10.3760/cma.j.issn.2095-0160.2017.05.005
Published 2017-05-10
Cite as Chin J Exp Ophthalmol, 2017,35(5): 410-415.

Abstract

Background

Acquired immune deficiency syndrome (AIDS) is an infectious disease caused by human immunodeficiency virus (HIV). Highly active antiretroviral therapy (HAART) is an effective treatment for AIDS, but it cannot completely eliminate the viral load in the body for the existence of HIV reservoir.Previous studies demonstrated that HIV could be detected in tears of virus load negative AIDS patients who received effective HAART, suggesting that lacrimal gland is another member of HIV reservoirs.

Objective

The aim of this study was to explore whether lacrimal gland has a molecular basis of HIV infection and the mechanism of lacrimal gland infection of HIV.

Methods

Fourteen specimens of lacrimal gland were collected during the surgery from 14 patients with lacrimal gland diseases in Peking Union Medical College Hospital from November 2013 to December 2015, including 13 non-HIV-infected patients and 1 HIV-infected patient.In 13 non-HIV infected patients, lacrimal glands prolapse was in 12 patients with the normal pathological tissue structure and dacryoadenitis was in 1 patient with the histopathological diagnosis of interstitial lymphoid tissue hyperplasia.The clinical manifestation of HIV-infected patient was dacryoadenitis with the histopathological diagnosis of interstitial lymphoid tissue hyperplasia.The paraffin sections of 12 non-HIV-infected specimens and 1 HIV-infected specimen were prepared, and the expressions of CD4, C-X-C chemokine receptor 4 (CXCR4)and C-C chemokine receptor type 5 (CCR5) in lacrimal gland specimens were detected by immunohistochemistry and verified in 1 specimen of non-HIV-infected specimen by immunofluorescence technology.

Results

Immunohistochemistry showed that CD4 was suspiciously positive expression in non-HIV-infected specimens with the strong background staining.CXCR4 was positively expressed in cytoplasm and nuclei of most lacrimal epithelial cells of lacrimal gland epithelial cells in each specimen, and CCR5 was focally expressed in few lacrimal gland epithelial cells in each specimen.In addition, CD4, CXCR4 and CCR5 were positively expressed in intercellular scattered lymphocytes on the specimens.Immunofluorescence assay showed that CD4, CXCR4 and CCR5 were expressed in the specimens with the red fluorescence, with the linear- and patchy-like distribution mainly in cellular membrane for CD4 or spot-like distribution for CXCR4 and CCR5 in the cytoplasm.

Conclusions

HIV receptor CD4 and accessory receptor CXCR4, CCR5 are positively expressed in the lacrimal gland epithelial cells, which is the molecular basis of HIV infection and become a potential HIV reservoir preventing HIV eradication.

Key words:

Acquired immunodeficiency syndrome/immunology; AIDS-associated ophthalmopathy/metabolism; HIV Infections/metabolism; Virus latency; Tears/virology; Receptors, CD4+ T-lymphocytes/virology; Receptors, CXCR4/metabolism; Receptors, CCR5/metabolism; Lacrimal gland epithelial cells

Contributor Information

Liu Ziyang
Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China
Liu Xiaowei
Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China
Ye Junjie
Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China
Han Yang
Department of Infection, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China
Li Taisheng
Department of Infection, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China
Huo Zhen
Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China
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