Macrophages as a Source of HIV During Opportunistic Infections

Orenstein, Jan M.; Fox, Cecil H.; Wahl, Sharon M.

doi:10.1126/science.276.5320.1857

Cited by 497 publications

(379 citation statements)

References 23 publications

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“…This finding is consistent with the knowledge that macrophages are a long-lived HIV reservoir, thereby providing a continuous source of virus for de novo infection of susceptible target cells that reside and/or circulate in the lymphoid tissue (35)(36)(37).…”

Section: Discussionsupporting

confidence: 90%

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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Section: Discussionsupporting

confidence: 90%

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

et al. 2000

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“…It is well-known that monocytes are refractory to HIV infection in vitro and in vivo. [37][38][39][40][41] This refractory property to HIV infection could be because monocytes express high levels of intracellular innate anti-HIV factors, including miRNAs. 23 We were particularly interested in miRNA-28, miRNA-125b, miRNA-150, miRNA-223, and miR-382 because these miRNAs can target a highly conserved region of HIV, present in all HIV clades.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Anti-HIV MicroRNA Expression

Wang

Zhou

et al. 2011

The American Journal of Pathology

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Several micro RNAs (miRNAs) have the ability to inhibit HIV replication in target cells. Thus, we investigated the impact of opioids (morphine and heroin), widely abused drugs among people infected with HIV, on the expression of cellular anti-HIV miRNAs in monocytes. We found that morphine-treated monocytes expressed lower levels of cellular anti-HIV miRNAs than untreated cells. In addition, morphine treatment of monocytes compromised type I interferon (IFN)-induced anti-HIV miRNA expression. These findings paralleled the observation that morphine treatment of monocytes enhanced HIV replication. These morphine-mediated actions on the anti-HIV miRNAs and HIV could be antagonized by the opioid receptor antagonists (naltrexone or Cys2, Tyr3, Arg5, Pen7-amide). Furthermore, the in vitro impact of morphine on miRNA expression was confirmed by the in vivo observation that heroin-dependent subjects had significantly lower levels of anti-HIV miRNAs (miRNA-28, 125b, 150, and 382) in peripheral blood mononuclear cells than the healthy subjects. These in vitro and in vivo findings indicate that opioid use impairs intracellular innate anti-HIV mechanism(s) in monocytes, contributing to cell susceptibility to HIV infection. (Am J

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“…Activated allogeneic lymphocytes reduce the expression of the C/EBP isoform in differentiated THP-1 and alveolar macrophages, increasing susceptibility to HIV-1 (Hoshino et al, 2002). This mechanism may operate in pathological conditions such as tuberculosis, which causes inflammation of the lungs (Orenstein et al, 1997).…”

Section: Viral Transcription In Macrophagesmentioning

confidence: 99%