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  1. Article ; Online: NF-κB sub-pathways and HIV cure

    Lilly M. Wong / Guochun Jiang

    EBioMedicine, Vol 63, Iss , Pp 103159- (2021)

    A revisit

    1478  

    Abstract: HIV cure is thwarted by the presence of quiescent yet replication competent HIV-1 (HIV). Antiretroviral therapy (ART) is unable to eradicate reservoirs, and upon cessation of ART, HIV will rebound. This review encompasses the curative strategies of HIV ... ...

    Abstract HIV cure is thwarted by the presence of quiescent yet replication competent HIV-1 (HIV). Antiretroviral therapy (ART) is unable to eradicate reservoirs, and upon cessation of ART, HIV will rebound. This review encompasses the curative strategies of HIV in the context of NF-κB sub-pathways that are currently exploited and demonstrate promise in the disruption of latent HIV. Canonical NF-κB signaling has long been established to drive HIV proviral expression while noncanonical NF-κB signaling, a novel and perhaps more desirable mechanism of latency reversal due to its unique characteristics, has recently been shown to also promote HIV expression from latency. Furthermore, we discuss the previously unrecognized upstream signaling of NF-κB as a new avenue for exploration of a functional cure of HIV.
    Keywords HIV latency ; Canonical NF-κB ; Noncanonical NF-κB ; PEBP1 ; Raf1 ; HIV cure ; Medicine ; R ; Medicine (General) ; R5-920
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: A Plausible Link of TMPRSS2/ACE2/AR Signaling to Male Mortality during the COVID-19 Pandemic in the United States

    Lilly M. Wong / Guochun Jiang

    Pathogens, Vol 10, Iss 1378, p

    2021  Volume 1378

    Abstract: The COVID-19 pandemic continues around the world, where the United States is among the worst in terms of both morbidity and fatality of the viral infection. We aim to investigate the plausible link of tissue SARS-CoV-2 viral entry gene expression, such ... ...

    Abstract The COVID-19 pandemic continues around the world, where the United States is among the worst in terms of both morbidity and fatality of the viral infection. We aim to investigate the plausible link of tissue SARS-CoV-2 viral entry gene expression, such as TMPRSS2 and ACE2, with infection and death by gender during the COVID-19 pandemic in the United States. We find a significantly higher incidence of COVID-19 death in men than in women, even though SARS-CoV-2 infection in women is higher than in men. We discover that the expression of TMPRSS2 and ACE2 in intestine, but not in lung, tends to be positively associated with the incidence of SARS-CoV-2 infection in men. In contrast, the high incidence of death in men is negatively correlated with TMPRSS2/ACE2 expression in intestine. Strikingly, the correlation of TMPRSS2/ACE2 expression with SARS-CoV-2 infection and death is the opposite in females, compared with that in males. Interestingly, male hormone signaling seems to be involved in mortality, as the low expression of testosterone receptor AR in the prostate contributes to death in men according to age. These observations point to a plausible contribution of male hormone metabolism in the regulation of TMPRSS2/ACE2 signaling to fatality by SARS-CoV-2 infection in men.
    Keywords COVID-19 ; SARS-Cov-2 ; TMPRSS2 ; ACE2 ; testosterone ; androgen receptor ; Medicine ; R
    Subject code 570
    Language English
    Publishing date 2021-10-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Lenalidomide downregulates ACE2 protein abundance to alleviate infection by SARS-CoV-2 spike protein conditioned pseudoviruses

    Siyuan Su / Jianfeng Chen / Ying Wang / Lilly M. Wong / Zhichuan Zhu / Guochun Jiang / Pengda Liu

    Signal Transduction and Targeted Therapy, Vol 6, Iss 1, Pp 1-

    2021  Volume 4

    Keywords Medicine ; R ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2021-05-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Crotonylation sensitizes IAPi-induced disruption of latent HIV by enhancing p100 cleavage into p52

    Dajiang Li / Morgan G. Dewey / Li Wang / Shane D. Falcinelli / Lilly M. Wong / Yuyang Tang / Edward P. Browne / Xian Chen / Nancie M. Archin / David M. Margolis / Guochun Jiang

    iScience, Vol 25, Iss 1, Pp 103649- (2022)

    2022  

    Abstract: Summary: The eradication of HIV infection is difficult to achieve because of stable viral reservoirs. Here, we show that crotonylation enhances AZD5582-induced noncanonical NF-κB (ncNF-κB) signaling, further augmenting HIV latency reversal in Jurkat and ... ...

    Abstract Summary: The eradication of HIV infection is difficult to achieve because of stable viral reservoirs. Here, we show that crotonylation enhances AZD5582-induced noncanonical NF-κB (ncNF-κB) signaling, further augmenting HIV latency reversal in Jurkat and U1 cell line models of latency, HIV latently infected primary CD4+ T cells and resting CD4+ T cells isolated from people living with HIV. Crotonylation upregulated the levels of the active p52 subunit of NF-κB following AZD5582. Biochemical analyses suggest that the ubiquitin E3 ligase TRIM27 is involved in enhanced p100 cleavage to p52. When TRIM27 was depleted, AZD5582-induced HIV latency reversal was reduced. TRIM27 small interfering RNA (siRNA) knockdown reduced both p100 and p52 levels without inhibiting p100 transcription, indicating that TRIM27 not only acts on p100 cleavage but also may impact p100/p52 stability. These observations reveal the complexity of HIV transcriptional machinery, particularly of NF-κB.
    Keywords Immunology ; Virology ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Brain microglia serve as a persistent HIV reservoir despite durable antiretroviral therapy

    Yuyang Tang / Antoine Chaillon / Sara Gianella / Lilly M. Wong / Dajiang Li / Theresa L. Simermeyer / Magali Porrachia / Caroline Ignacio / Brendon Woodworth / Daniel Zhong / Jiayi Du / Eduardo de la Parra Polina / Jennifer Kirchherr / Brigitte Allard / Matthew L. Clohosey / Matt Moeser / Amy L. Sondgeroth / Gregory D. Whitehill / Vidisha Singh /
    Amir Dashti / Davey M. Smith / Joseph J. Eron / Katherine J. Bar / Ann Chahroudi / Sarah B. Joseph / Nancie M. Archin / David M. Margolis / Guochun Jiang

    The Journal of Clinical Investigation, Vol 133, Iss

    2023  Volume 12

    Abstract: Brain microglia (MG) may serve as a human immunodeficiency virus 1 (HIV) reservoir and ignite rebound viremia following cessation of antiretroviral therapy (ART), but they have yet to be proven to harbor replication-competent HIV. Here, we isolated brain ...

    Abstract Brain microglia (MG) may serve as a human immunodeficiency virus 1 (HIV) reservoir and ignite rebound viremia following cessation of antiretroviral therapy (ART), but they have yet to be proven to harbor replication-competent HIV. Here, we isolated brain myeloid cells (BrMCs) from nonhuman primates and rapid autopsy of people with HIV (PWH) on ART and sought evidence of persistent viral infection. BrMCs predominantly displayed microglial markers, in which up to 99.9% of the BrMCs were TMEM119+ MG. Total and integrated SIV or HIV DNA was detectable in the MG, with low levels of cell-associated viral RNA. Provirus in MG was highly sensitive to epigenetic inhibition. Outgrowth virus from parietal cortex MG in an individual with HIV productively infected both MG and PBMCs. This inducible, replication-competent virus and virus from basal ganglia proviral DNA were closely related but highly divergent from variants in peripheral compartments. Phenotyping studies characterized brain-derived virus as macrophage tropic based on the ability of the virus to infect cells expressing low levels of CD4. The lack of genetic diversity in virus from the brain suggests that this macrophage-tropic lineage quickly colonized brain regions. These data demonstrate that MG harbor replication-competent HIV and serve as a persistent reservoir in the brain.
    Keywords AIDS/HIV ; Medicine ; R
    Subject code 616
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher American Society for Clinical Investigation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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