The Association of Human Cytomegalovirus with Biomarkers of Inflammation and Immune Activation in HIV-1-Infected Women

Lurain, Nell S.; Hanson, Barbara A.; Hotton, Anna L.; Weber, Kathleen M.; Cohen, Mardge H.; Landay, Alan

doi:10.1089/aid.2015.0169

Cited by 36 publications

(38 citation statements)

References 54 publications

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“…Similarly, among women on ART for a median of 4-5 months, we noted that elevated post-ART CMV IgG antibody levels were associated with higher plasma immune activation markers. There is considerable variability between studies in precisely which immune activation markers are associated with post-ART CMV IgG levels [11, 13, 26, 44-47] , but our findings are consistent with the model suggesting that CMV has a role in driving persistent immune activation during suppressive ART [25] . The durability of these associations require confirmation during long-term ART use.…”

Section: Discussionsupporting

confidence: 87%

“…Numerous investigations have suggested that CMV replication continues to drive CD8 + T-cell expansion and inflammation in ART-experienced individuals [20-25] . The cross-sectional evidence is conflicting in untreated and treated HIV-infected individuals, but some studies suggest CMV IgG antibody levels may also be associated with immune activation markers, such as C-reactive protein (CRP) [13] , a general biomarker of systemic inflammation, and soluble CD14 (sCD14) [26] ,a biomarker of nonspecific monocyte activation [27] .…”

Section: Introductionmentioning

confidence: 99%

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Elevated cytomegalovirus IgG antibody levels are associated with HIV-1 disease progression and immune activation

Patel¹,

Gianella

Newell³

et al. 2017

Aids

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Objective To assess the association between CMV IgG antibody levels, HIV disease progression, and immune activation in sub-Saharan Africa. Design A prospective cohort study was conducted among women enrolled in a trial that was designed to determine the effect of acyclovir on HIV disease progression in Rakai, Uganda. Methods The primary endpoints were progression to a CD4+ T-cell count<250 cells/μL, non-traumatic death, or initiation of ART. CD4+ T-cell counts, HIV viral load, C-reactive protein, and soluble CD14 levels were assessed biannually for 24 months. CMV IgG antibody were measured at baseline among all women, and annually among a subset of women who initiated ART during the study. Results There were 300 HIV/CMV coinfected participants who contributed a total of 426.4 person-years with a median follow-up time of 1.81 years. Compared to the lowest CMV IgG tertile group at baseline, the highest CMV IgG tertile group was associated with an increased risk to reach a primary endpoint independent of acyclovir use, age, CD4+ T-cell count, and HIV viral load at baseline (adjHR=1.59;[95%CI=1.05-2.39];P=0.027). Among pre-ART visits (n=1,200), women in the highest baseline CMV IgG tertile had increasing annual rates of sCD14 and CRP levels, which was not observed for the low CMV IgG tertile group. Compared to pre-ART visits, CMV IgG antibody levels were higher post-ART initiation, and concurrent levels remained associated with sCD14 and CRP during suppressive ART (n=95). Conclusion The magnitude of the immune response to CMV was associated with HIV disease progression and immune activation in sub-Saharan Africa.

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Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Elevated cytomegalovirus IgG antibody levels are associated with HIV-1 disease progression and immune activation

Patel¹,

Gianella

Newell³

et al. 2017

Aids

View full text Add to dashboard Cite

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“…DNA was extracted from the pooled monolayers using the Blood gDNA kit (Promega, Madison, WI). HCMV DNA was quantitated using a validated in-house assay, which targets the DNA polymerase 30 . Reactions were performed on an Applied Biosystems 7500 (Thermo Fisher Scientific).…”

Section: Viral Stock Preparationmentioning

confidence: 99%

Ginkgolic acid inhibits fusion of enveloped viruses

Borenstein

Hanson

Markosyan

et al. 2020

Sci Rep

Self Cite

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Ginkgolic acids (GA) are alkylphenol constituents of the leaves and fruits of Ginkgo biloba. GA has shown pleiotropic effects in vitro, including: antitumor effects through inhibition of lipogenesis; decreased expression of invasion associated proteins through AMPK activation; and potential rescue of amyloid-β (Aβ) induced synaptic impairment. GA was also reported to have activity against Escherichia coli and Staphylococcus aureus. Several mechanisms for this activity have been suggested including: SUMOylation inhibition; blocking formation of the E1-SUMO intermediate; inhibition of fatty acid synthase; non-specific SIRT inhibition; and activation of protein phosphatase type-2C. Here we report that GA inhibits Herpes simplex virus type 1 (HSV-1) by inhibition of both fusion and viral protein synthesis. Additionally, we report that GA inhibits human cytomegalovirus (HCMV) genome replication and Zika virus (ZIKV) infection of normal human astrocytes (NHA). We show a broad spectrum of fusion inhibition by GA of all three classes of fusion proteins including HIV, Ebola virus (EBOV), influenza A virus (IAV) and Epstein Barr virus (EBV). In addition, we show inhibition of a non-enveloped adenovirus.Our experiments suggest that GA inhibits virion entry by blocking the initial fusion event. Data showing inhibition of HSV-1 and CMV replication, when GA is administered post-infection, suggest a possible secondary mechanism targeting protein and DNA synthesis. Thus, in light of the strong effect of GA on viral infection, even after the infection begins, it may potentially be used to treat acute infections (e.g. Coronavirus, EBOV, ZIKV, IAV and measles), and also topically for the successful treatment of active lesions (e.g. HSV-1, HSV-2 and varicella-zoster virus (VZV)).Ginkgolic acids are alkylphenol constituents of the leaves and fruits of Ginkgo biloba. Ginkgo biloba extracts (GBE) have been used as herbal supplements since at least the 16 th century and remain widely in use 1 . Major constituents of GBE include terpine trilactones (ginkgolide A, B, C, J, and bilobalide), flavonoid glycosides (quercetin and rutin), as well as Ginkgolic acids 2 . Ginkgolic acids are a mixture of several 2-hydroxy-6-alkylbenzoic acids in which the most common alkyl chains contain 13, 15, or 17 carbons. The 15 and 17 carbon chains are unsaturated at positions 8 and 10, respectively. The 3 Ginkgolic acid (GA) structures are, therefore, designated C13:0, C15:1, and C17:1 (Table S1) 3 .GA has shown pleiotropic effects in vitro, including: antitumor effects through inhibition of lipogenesis; decreased expression of invasion associated proteins through AMPK activation; potential rescue of amyloid-β (Aβ) induced synaptic impairment; and inhibition of HIV protease activity as well as HIV viral replication 4-7 . GA was also reported to have activity against Escherichia coli and Staphylococcus aureus 8 . Several ways in which GA works have been suggested including by SUMOylation inhibition activity; blocking formation of the E1-SUMO intermediate 9 ;...

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“…In the general population, CMV has been associated with both subclinical and clinical CVD [125, 126]. In HIV, CMV antibody levels are associated with increased IL-6 and sCD14 levels [127], sCD163 [75], coronary plaque burden on CCTA [27], and prevalence of carotid artery lesions [128]. Additionally, higher CMV-specific T-cell responses in co-infected patients have been associated with increased CIMT in some [129] but not all studies [82].…”

Section: Causes Of Chronic Inflammation In Patients With Hivmentioning

confidence: 99%