Tumor necrosis factor alpha functions in an autocrine manner in the induction of human immunodeficiency virus expression.

Poli, Guido; Kinter, Audrey; Justement, J. Shawn; Kehrl, John H.; Bressler, Peter; Stanley, Sharilyn K.; Fauci, Anthony S.

doi:10.1073/pnas.87.2.782

Cited by 423 publications

(246 citation statements)

References 32 publications

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“…Upon phosphorylation, IκB disassociates from the NF-κB and is degraded by the proteosome, allowing free NF-κB to translocate into the nucleus to stimulate transcription. TNF-α is a potent activator of NF-κB and HIV-1 LTR expression (41). After 5 min of treatment with TNF-α, phospho-IκB appeared rapidly, and a subsequent decrease in total IκB was evident after 30 min incubation (Fig.…”

Section: Resultsmentioning

confidence: 99%

Neisseria gonorrhoeae-derived heptose elicits an innate immune response and drives HIV-1 expression

Malott¹,

Keller

Gaudet³

et al. 2013

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

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Clinical and epidemiological synergy exists between the globally important sexually transmitted infections, gonorrhea and HIV. Neisseria gonorrhoeae , which causes gonorrhea, is particularly adept at driving HIV-1 expression, but the molecular determinants of this relationship remain undefined. N. gonorrhoeae liberates a soluble factor that potently induces expression from the HIV-1 LTR in coinfected cluster of differentiation 4-positive (CD4 + ) T lymphocytes, but this factor is not a previously described innate effector. A genome-wide mutagenesis approach was undertaken to reveal which component(s) of N. gonorrhoeae induce HIV-1 expression in CD4 + T lymphocytes. A mutation in the ADP-heptose biosynthesis gene, hldA , rendered the bacteria unable to induce HIV-1 expression. The hldA mutant has a truncated lipooligosaccharide structure, contains lipid A in its outer membrane, and remains bioactive in a TLR4 reporter-based assay but did not induce HIV-1 expression. Mass spectrometry analysis of extensively fractionated N. gonorrhoeae- derived supernatants revealed that the LTR-inducing fraction contained a compound having a mass consistent with heptose-monophosphate (HMP). Heptose is a carbohydrate common in microbes but is absent from the mammalian glycome. Although ADP-heptose biosynthesis is common among Gram-negative bacteria, and heptose is a core component of most lipopolysaccharides, N. gonorrhoeae is peculiar in that it effectively liberates HMP during growth. This N. gonorrhoeae- derived HMP activates CD4 + T cells to invoke an NF-κB–dependent transcriptional response that drives HIV-1 expression and viral production. Our study thereby shows that heptose is a microbial-specific product that is sensed as an innate immune agonist and unveils the molecular link between N. gonorrhoeae and HIV-1.

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Section: Resultsmentioning

confidence: 99%

Neisseria gonorrhoeae-derived heptose elicits an innate immune response and drives HIV-1 expression

Malott¹,

Keller

Gaudet³

et al. 2013

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

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“…Consequently, HIV-1 proviral integration sites for ACH2 cells and NCHA 1, 2 cell lines were very unique as follows (Table 1): NT5C3 gene on chromosome 7 for ACH2 cells, BC007278 gene on chromosome 2 and unknown gene on chromosome X for NCHA1 cell line, and AK096155 gene on chromosome 11 for NCHA2 cell line. ACH2 cells have been already reported to contain a single copy of HIV-1 provirus (Poli et al, 1990). Ishida et al (2006) firstly identified the flanking sequence of HIV-1 provirus integrated into ACH2 cells by inverse PCR and this sequence corresponded to the sequence of NT5C3 gene on the chromosome 7 by NCBI blast program.…”

Section: Resultsmentioning

confidence: 99%

Establishment of novel cell lines latently infected with human immunodeficiency virus 1

Oh¹,

Kim²,

Hong³

et al. 2011

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“…A high concentration of TNF-a may be expected to contribute to the cachexia commonly seen in the Ethiopian paiients. Also, TNF-a is an aclivalor of HIV replication [35,36], and an early production of this cytokine might accelerate the progression of the HIV infection. On the other hand, IFN-a is known lo downregulate the release of HIV [37], and a failure to produce sufficient amounts of IFN-a may result in an inability lo contain the infection.…”

Section: ]mentioning

confidence: 99%

Raised levels of tumour necrosis factor-alpha and neopterin, but not interferon-alpha, in serum of HIV-1-infected patients from Ethiopia

Ayehunie

Sönnerborg²,

Yemane-Berhan

et al. 1993

Clinical and Experimental Immunology

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SUMMARY Serum levels of tumour necrosis factor‐alpha (TNF‐α). neopterin and interferon‐alpha (IFN‐α) were determined by immunoradiometric assays in 60 HIV‐1+and 20 HIV‐1− subjects from Ethiopia. Swedish samples were used as reference material. The Ethiopian HIV‐1‘ subjects were found to have significantly increased TNF‐α and neopterin, but not IFN‐α levels. Increased levels of TNF‐α and neopterin were frequently found in Ethiopian asymptomatic subjects (37% and 41%). and the concentration increased in patients with AIDS (83% and 90% respectively). The levels of the two substances and the proportion of patients with higher TNF‐α values were lower in the corresponding Swedish subjects. The proportion of sera with raised levels of I FN‐α was very low (asymptomatic 4%, and AIDS 7%) in Ethiopian subjects. These results suggest a very early increase in the TNF‐α production and activation of the cellular immune response, and a low level of IFN‐α synthesis in the natural course of HIV infection in Ethiopia. The aberrations may contribute to a rapid progress of immunodeficiency and cachexia often seen in Ethiopian patients.

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Tumor necrosis factor alpha functions in an autocrine manner in the induction of human immunodeficiency virus expression.

Cited by 423 publications

References 32 publications

Neisseria gonorrhoeae-derived heptose elicits an innate immune response and drives HIV-1 expression

Neisseria gonorrhoeae-derived heptose elicits an innate immune response and drives HIV-1 expression

Establishment of novel cell lines latently infected with human immunodeficiency virus 1

Raised levels of tumour necrosis factor-alpha and neopterin, but not interferon-alpha, in serum of HIV-1-infected patients from Ethiopia

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