Long‐term efficient control of <scp>SIV</scp> infection in macaques is associated with an intact intestinal barrier

Daskalaki, Maria; Neumann, Berit; Klippert, Antonina; Mätz‐Rensing, Kerstin; Kaup, Franz‐Josef; Stahl–Hennig∥, Christiane

doi:10.1111/jmp.12294

Cited by 2 publications

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“…In order to analyze which DNA methylation profiles are associated with uncontrolled viremia and immune activation, we compared viremic MAC to two non-progressive animal models: SIV-infected AGM and SIV controller MAC. SIV controller MAC mimic humans who can spontaneously control HIV [28,29]. In these three non-human primate models, we investigated whether SIV infection-induced changes in DNA methylation occurred in genes associated with (1) immune activation and regulation; (2) T cell differentiation; (3) anti-viral immune responses such as viral restriction factors; (4) antigen-presentation; (5) cell metabolism; and (6) cell proliferation.…”

Section: Introductionmentioning

confidence: 99%

DNA methylation changes in metabolic and immune-regulatory pathways in blood and lymph node CD4 + T cells in response to SIV infections

et al. 2020

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The molecular mechanisms underlying HIV-induced inflammation, which persists even during effective long-term treatment, remain incompletely defined. Here, we studied pathogenic and nonpathogenic simian immunodeficiency virus (SIV) infections in macaques and African green monkeys, respectively. We longitudinally analyzed genome-wide DNA methylation changes in CD4 + T cells from lymph node and blood, using arrays. DNA methylation changes after SIV infection were more pronounced in lymph nodes than blood and already detected in primary infection. Differentially methylated genes in pathogenic SIV infection were enriched for Th1-signaling (e.g., RUNX3, STAT4, NFKB1) and metabolic pathways (e.g., PRKCZ). In contrast, nonpathogenic SIVagm infection induced DNA methylation in genes coding for regulatory proteins such as LAG-3, arginase-2, interleukin-21 and interleukin-31. Between 15 and 18% of genes with DNA methylation changes were differentially expressed in CD4 + T cells in vivo. Selected identified sites were validated using bisulfite pyrosequencing in an independent cohort of uninfected, viremic and SIV controller macaques. Altered DNA methylation was confirmed in blood and lymph node CD4 + T cells in viremic macaques but was notably absent from SIV controller macaques. Our study identified key genes differentially methylated already in primary infection and in tissues that could contribute to the persisting metabolic disorders and inflammation in HIV-infected individuals despite effective treatment.

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Section: Introductionmentioning

confidence: 99%

DNA methylation changes in metabolic and immune-regulatory pathways in blood and lymph node CD4 + T cells in response to SIV infections

et al. 2020

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SIV-induced terminally differentiated adaptive NK cells in lymph nodes associated with enhanced MHC-E restricted activity

et al. 2021

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Natural killer (NK) cells play a critical understudied role during HIV infection in tissues. In a natural host of SIV, the African green monkey (AGM), NK cells mediate a strong control of SIVagm infection in secondary lymphoid tissues. We demonstrate that SIVagm infection induces the expansion of terminally differentiated NKG2alow NK cells in secondary lymphoid organs displaying an adaptive transcriptional profile and increased MHC-E-restricted cytotoxicity in response to SIV Env peptides while expressing little IFN-γ. Such NK cell differentiation was lacking in SIVmac-infected macaques. Adaptive NK cells displayed no increased NKG2C expression. This study reveals a previously unknown profile of NK cell adaptation to a viral infection, thus accelerating strategies toward NK-cell directed therapies and viral control in tissues.

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Long‐term efficient control of SIV infection in macaques is associated with an intact intestinal barrier

Cited by 2 publications

References 18 publications

DNA methylation changes in metabolic and immune-regulatory pathways in blood and lymph node CD4 + T cells in response to SIV infections

DNA methylation changes in metabolic and immune-regulatory pathways in blood and lymph node CD4 + T cells in response to SIV infections

SIV-induced terminally differentiated adaptive NK cells in lymph nodes associated with enhanced MHC-E restricted activity

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