Rapid Infection of Oral Mucosal-Associated Lymphoid Tissue with Simian Immunodeficiency Virus

Stahl–Hennig∥, Christiane; Steinman, Ralph M.; Tenner-Rácz, Klara; Pope, Melissa; Stolte, Nicole; Mätz‐Rensing, Kerstin; Groβschupff, Gudrun; Raschdorff, Birgit; Hunsmann, Gerhard; Rácz, Paul

doi:10.1126/science.285.5431.1261

Cited by 221 publications

(163 citation statements)

References 28 publications

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“…In a simian model of infection, simian immunodeficiency virus has been shown to spread from the pluristratified squamous epithelium of the tonsils quickly to other lymphoid organs. 44 Whatever the site of HTLV-1 entry through the digestive tract (eg, tonsils, gut, etc), the present study provides the first evidence for mechanisms of HTLV-1 passage through a tight epithelium. In addition, our model provides a platform with which to study the different factors that could modulate such a passage, such as lactoferrin, 45 maternal Ab titer, 46 and proviral load, 47,48 to gain an understanding of the nature of the mother-to-child transmission of HTLV-1.…”

Section: Htlv-1 Passage Across Human Epithelial Barrier 577mentioning

confidence: 85%

Transcytosis of HTLV-1 across a tight human epithelial barrier and infection of subepithelial dendritic cells

Martin‐Latil

Gnädig

Mallet

et al. 2012

Blood

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Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma and HTLV-1-associated myelopathy/tropical spastic paraparesis. In addition to blood transfusion and sexual transmission, HTLV-1 is transmitted mainly through prolonged breastfeeding, and such infection represents a major risk for the development of adult T-cell leukemia/lymphoma. Although HTLV-1-infected lymphocytes can be retrieved from maternal milk, the mechanisms of HTLV-1 transmission through the digestive tract remain unknown. In the present study, we assessed HTLV-1 transport across the epithelial barrier using an in vitro model. Our results show that the integrity of the epithelial barrier was maintained during coculture with HTLV-1-infected lymphocytes, because neither morphological nor functional alterations of the cell monolayer were observed. Enterocytes were not susceptible to HTLV-1 infection, but free infectious HTLV-1 virions could cross the epithelial barrier via a transcytosis mechanism.Such virions were able to infect productively human dendritic cells located beneath the epithelial barrier. Our data indicate that HTLV-1 crosses the tight epithelial barrier without disruption or infection of the epithelium to further infect target cells such as dendritic cells. The present study provides the first data pertaining to the mode of HTLV-1 transport across a tight epithelial barrier, as can occur during mother-to-child HTLV-1 transmission during breastfeeding. IntroductionApproximately 5-20 million persons worldwide are infected by the human retrovirus human T-cell leukemia virus type 1 (HTLV-1), 1 and this virus is the causative agent of severe adult T-cell leukemia/lymphoma 2 and inflammatory syndromes such as tropical spastic paraparesis/HTLV-1-associated myelopathy, a slowly progressing neurodegenerative disease that occurs in 0.5%-3% of infected persons. 3 HTLV-1 is transmitted via sexual intercourse, by transfusion with contaminated blood, and from mother to child. The latter constitutes 15%-25% of overall transmission, so it is a major method of viral spread. 4,5 Although intrauterine or perinatal transmission during birth cannot be excluded, breastfeeding is the main pathway of HTLV-1 transmission in highly endemic areas such as intertropical Africa, the Caribbean, or regions of South America. 6,7 Milk-borne transmission is supported by the presence of high levels of infected lymphocytes in maternal milk, 10 5 -10 7 of these being transferred to the child at each feed, 8,9 in addition to infected macrophages and breast epithelial cells. Furthermore, leukocytes in the breast milk remain viable after ingestion for up to 4 hours because of the buffering capacity of breast milk and the low acidity of the neonatal child's stomach. 10,11 The risk of transmission increases with the time that children are breastfed, especially when this exceeds 6 months. In addition to the duration of breastfeeding, the mother's age, Ab titers directed against HTLV-1 antigens, proviral load in the PBMCs and milk, a...

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Section: Htlv-1 Passage Across Human Epithelial Barrier 577mentioning

confidence: 85%

Transcytosis of HTLV-1 across a tight human epithelial barrier and infection of subepithelial dendritic cells

Martin‐Latil

Gnädig

Mallet

et al. 2012

Blood

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“…The latter are a highly specialized cellular component of the mucosa-associated lymphoid tissue that acts as a gateway for various antigens that are present in the body cavities, like the nasopharynx (33). Such antigens are processed and/or forwarded through the cytoplasmic invaginations of M-cells, which subsequently present them to the various immune effector cells circulating in the lowest part of the lymphoepithelium (14,(32)(33)(34). In keeping with the findings of Fais et al (31), we can therefore speculate that MGCs probably result from the transmigration and homotypic fusion of blood monocytes that are infected by HIV present in the nasopharyngeal secretions during the circulation of these cells in the lymphoepithelium area.…”

Section: Discussionmentioning

confidence: 99%

HIV-Associated Multinucleated Giant Cells in Lymphoid Tissue of the Waldeyer's Ring: A Detailed Study

et al. 2000

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Hyperplastic lymphoid tissues of the Waldeyer's ring in human immunodeficiency virus (HIV)-infected patients may occasionally contain multinucleated giant cells (MGCs). These cells, which are unrelated to any opportunistic infection, previously have been demonstrated to harbor significant amounts of HIV. Studies undertaken to characterize these MGCs have generated conflicting results: some reports suggested a macrophage origin, whereas others supported a dendritic cell lineage. This study was performed to determine the occurrence of MGCs in a series of adenoid/tonsil specimens from HIV-seropositive patients showing no histological evidence of opportunistic infection in order to further characterize the phenotype of these cells and to investigate the role of a viral infection in their pathogenesis. Adenoid/tonsil tissue specimens from 21 HIV-seropositive patients with no documented opportunistic infection were scrutinized for the presence of MGCs and evaluated immunohistochemically on paraffin sections by antibodies directed against various macrophage and DC antigens. These antigens included CD68, the macrophage marker 3A5, major histocompatibility complex Class II, S-100 protein, CD1a, and CD83. Additional immunostainings directed at CD21 and CD35 as well as at the HIV-associated p24 antigen were also performed. Finally, the presence of Epstein-Barr virus and human herpesvirus 8 viral sequences was investigated by in situ hybridization and by polymerase chain reaction analysis, respectively. MGCs were found in 14 patients (66.7%), regardless of gender, age, method of viral transmission, CD4 cell count, viral load, or ethnic group. These cells were mostly localized at the lymphoepithelium layer of the tonsillar crypts and, to a lesser extent, in the interfollicular areas of the underlying lymphoid tissue, which consistently exhibited features of follicular hyperplasia. Phenotypically, MGCs were found to be CD68 ؉ , 3A5 ؉ , major histocompatibility complex Class II ؉ , S-100 protein ؉/؊ , CD1a ؊ , CD21 ؊ , CD35 ؊ , and CD83 ؊ . Although the HIV-associated p24 protein was consistently present in the cytoplasm of these cells, no sign of Epstein-Barr virus or human herpesvirus 8 infection could be demonstrated. Consequently, our study didn't show any conclusive evidence to support that MGCs in hyperplastic lymphoid tissues of the Waldeyer's ring from HIV-seropositive patients originated from dendritic cells. The definite nature of these cells has yet to be elucidated, but it is plausible that they simply represent activated macrophages that are infected with HIV present in the oropharyngeal secretions during the circulation of their precursor through the lymphoepithelium area of adenoids and tonsils.

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“…In addition, DC-SIGN also interacts with the intercellular adhesion molecule-3 receptor expressed on T cells, thereby contributing to the close interaction between DCs and T cells required for efficient antigen presentation (22). Because dendritic cells are among the first cells encountered by HIV-1 during sexual transmission, it is possible that virus bound by DC-SIGN may be ultimately ferried to lymph nodes (a major site of viral replication) as a consequence of the normal cellular trafficking of DCs (23,24). In fact, virus bound to DCs remains infectious for at least several days (15).…”

mentioning

confidence: 99%

DC-SIGNR, a DC-SIGN homologue expressed in endothelial cells, binds to human and simian immunodeficiency viruses and activates infection in trans

Pöhlmann

Soilleux²,

Baribaud³

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

304

302

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Rapid Infection of Oral Mucosal-Associated Lymphoid Tissue with Simian Immunodeficiency Virus

Cited by 221 publications

References 28 publications

Transcytosis of HTLV-1 across a tight human epithelial barrier and infection of subepithelial dendritic cells

Transcytosis of HTLV-1 across a tight human epithelial barrier and infection of subepithelial dendritic cells

HIV-Associated Multinucleated Giant Cells in Lymphoid Tissue of the Waldeyer's Ring: A Detailed Study

DC-SIGNR, a DC-SIGN homologue expressed in endothelial cells, binds to human and simian immunodeficiency viruses and activates infection in trans

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