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Epigenetic modification of FOXP3 in patients with chronic HIV infection.

ABSTRACT: OBJECTIVES:HIV-1 modulates host cell epigenetic machinery to control its own replication and induce immune suppression. HIV-1 infection leads to activation of T regulatory cell (T(reg)), but the mechanism underlying this immune modulation is unclear. T(reg) plays a prominent role in gut-mucosal immune tolerance by restraining excessive effector T-cell responses, a mechanism that is known to be disturbed in chronic HIV-1 infection. DNA methylation plays a major role in T(reg) lineage commitment and immune homeostasis, which may be regulated by HIV. To investigate the mechanisms of aberrant methylation of the T(reg) marker FOXP3 in HIV-1 infection, we evaluated the expression pattern of methylation-related enzymes and its correlation to FOXP3 methylation. METHODS:FOXP3 promoter methylation in the colon mucosa and peripheral blood from HIV-infected patients and control subjects was measured using Pyrosequencing. Gene expression pattern of DNA methylation enzymes in the colon mucosa was investigated by Microarray and quantitative reverse transcriptase-polymerase chain reaction analysis in the same subjects. RESULTS:FOXP3 promoter was significantly (P ? 0.0001) demethylated in HIV-infected patients compared with control subjects in both tissues. Expression of DNA methyltransferase 1 (DNAMT1), DNA methyltransferase 1-associated protein 1(DMAP1), methyltransferase-like 7B (METTL7B), and methyltransferase-like 10 (METTL10) were significantly down regulated in HIV-infected patients compared with controls and had a significant positive correlation to FOXP3 promoter methylation. CONCLUSIONS:We present evidence suggesting that altered methylation pattern of FOXP3 and accordingly higher T(reg) frequency in gut mucosa of HIV-infected patients may be because of aberrant methylation processing in HIV.

SUBMITTER: Abdel-Hameed EA

PROVIDER: S-EPMC3871978 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Epigenetic modification of FOXP3 in patients with chronic HIV infection.

Abdel-Hameed Enass A EA Ji Hong H Sherman Kenneth E KE Shata Mohamed T M MT

Journal of acquired immune deficiency syndromes (1999) 20140101 1

<h4>Objectives</h4>HIV-1 modulates host cell epigenetic machinery to control its own replication and induce immune suppression. HIV-1 infection leads to activation of T regulatory cell (T(reg)), but the mechanism underlying this immune modulation is unclear. T(reg) plays a prominent role in gut-mucosal immune tolerance by restraining excessive effector T-cell responses, a mechanism that is known to be disturbed in chronic HIV-1 infection. DNA methylation plays a major role in T(reg) lineage comm ...[more]

PMID: 23846566

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Project description:The prevalence of HIV-associated chronic kidney disease (CKD) varies geographically and depends on the definition of CKD used, ranging from 4.7% to 38% globally. The incidence, however, has decreased with the use of effective combined antiretroviral therapy (cART). A wide variety of histological patterns are seen in HIV-associated kidney diseases that include glomerular and tubulointerstitial pathology. In resource-rich settings, there has been a plateau in the incidence of end-stage renal disease secondary to HIV-associated nephropathy (HIVAN). However, the prevalence of end-stage renal disease in HIV-positive individuals has risen, mainly due to increased longevity on cART. There is a disparity in the occurrence of HIVAN among HIV-positive individuals such that there is an 18- to 50-fold increased risk of developing kidney disease among HIV-positive individuals of African descent aged between 20 and 64 years and who have a poorer prognosis compared with their European descent counterparts, suggesting that genetic factors play a vital role. Other risk factors include male sex, low CD4 counts, and high viral load. Improvement in renal function has been observed after initiation of cART in patients with HIV-associated CKD. Treatment with an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker is recommended, when clinically indicated in patients with confirmed or suspected HIVAN or clinically significant albuminuria. Other standard management approaches for patients with CKD are recommended. These include addressing other cardiovascular risk factors (appropriate use of statins and aspirin, weight loss, cessation of smoking), avoidance of nephrotoxins, and management of serum bicarbonate and uric acid, anemia, calcium, and phosphate abnormalities. Early diagnosis of kidney disease by screening of HIV-positive individuals for the presence of kidney disease is critical for the optimal management of these patients. Screening for the presence of kidney disease upon detection of HIV infection and annually thereafter in high-risk populations is recommended.

Dataset Information

Epigenetic modification of FOXP3 in patients with chronic HIV infection.

Publications

Epigenetic modification of FOXP3 in patients with chronic HIV infection.

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