記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：STAR Protocols  

Eradication of HIV-1 latently infected cells is an important issue in HIV treatment. However, there are limited models available to assess therapeutic efficacy in vitro. Here, we present a protocol for establishing a variety of HIV-infected Jurkat cells, including productive and latent status, evaluating the efficacy of antiviral agents, followed by PCR/sequencing-based detection of replication competent HIV provirus. This protocol is useful for optimization of treatment of HIV-1 and provides insights into the mechanisms of clonal selection of heterogeneous HIV-1-infected cells. For complete details on the use and execution of this protocol, please refer to Matsuda et al. (2021).1

DOI： 10.1016/j.xpro.2023.102547

Scopus

PubMed

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：European Journal of Medicinal Chemistry  

Cells latently infected with human immunodeficiency virus type 1 (HIV-1) prevent people living with HIV-1 from obtaining a cure to the infectious disease. Latency reversing agents (LRAs) such as protein kinase C (PKC) activators and histone deacetylase (HDAC) inhibitors can reactivate cells latently infected with HIV-1. Several trials based on treatment with HDAC inhibitors alone, however, failed to reduce the number of latent HIV-1 reservoirs. Herein, we have focused on a diacylglycerol (DAG)-lactone derivative, YSE028 (1), which is a PKC activator with latency reversing activity and no significant cytotoxicity. Caspase-3 activation of YSE028 (1) led to cell apoptosis, specifically in HIV-1 latently infected cells. Structure-activity relationship studies of YSE028 (1) have produced several useful derivatives. Among these, compound 2 is approximately ten times more potent than YSE028 (1) in reactivation of cells latently infected with HIV-1. The activity of DAG-lactone derivatives was correlated with the binding affinity for PKC and the stability against esterase-mediated hydrolysis.

DOI： 10.1016/j.ejmech.2023.115449

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PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Although vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease 2019 (COVID-19) induce effective immune responses, vaccination with booster doses is necessary because of waning immunity. We conducted an open-label, non-randomized, single-arm study in adults in Japan to assess the immunogenicity and safety of a single booster dose of the KD-414 purified whole-SARS-CoV-2-virion inactivated vaccine candidate after vaccination with a primary series of BNT162b2. The primary endpoint was serum neutralizing activity at 7 days after booster injection compared with the primary series of BNT162b2. The SARS-CoV-2-structural protein-binding antibody level and T cell response against SARS-CoV-2-Spike (S) peptides were also examined as secondary endpoints, and safety profile assessments were conducted. Twenty subjects who participated in a previous study declined an injection of KD-414 (non-KD-414 group) and received a booster dose of BNT162b2 instead. The non-KD-414 group was compared to the KD-414 group as a secondary outcome. A single dose of KD-414 induced lower serum neutralizing activity against the wild-type virus within 7 days compared to after the primary series of BNT162b2 but significantly induced anti-SARS-CoV-2-S1-receptor-binding domain-binding immunoglobulin G (IgG) antibodies and SARS-CoV-2-S peptide-specific CD4+ and CD8+ T cell responses. Local or systemic symptoms were significantly lower in the participants who received KD-414 than in those who received BNT162b2 as the third COVID-19 vaccine dose. The present data indicate that a single booster dose of KD-414 induces a substantial immune response in BNT162b2-primed individuals and has a good safety profile, thereby supporting further clinical trials to identify rational targets.

DOI： 10.1080/21645515.2023.2193074

PubMed

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：International Journal of Infectious Diseases  

Objectives: To investigate the role of immunogenicity after the third vaccine dose against Omicron infection and COVID-19-compatible symptoms of infection. Methods: First, we examined vaccine effectiveness (VE) of the third dose against the second dose during the Omicron wave among the staff at a tertiary hospital in Tokyo. In a case-control study of third vaccine recipients, we compared the preinfection live-virus neutralizing antibodies (NAb) against Omicron between breakthrough cases and their controls who had close contact with patients with COVID-19. Among these cases, we examined the association between NAb levels and the number of COVID-19-compatible symptoms. Results: Among the 1456 participants for VE analysis, 60 breakthrough infections occurred during the Omicron wave. The third dose VE for infection was 54.6%. Among the third dose recipients, NAb levels against Omicron did not differ between the cases (n = 22) and controls (n = 21). Among the cases, those who experienced COVID-19-compatible symptoms had lower NAb levels against Omicron than those who did not. Conclusion: The third vaccine dose was effective in decreasing the risk of SARS-CoV-2 infection during Omicron wave compared with the second dose. Among third dose recipients, higher preinfection NAb levels may not be associated with a lower risk of Omicron infection. Contrarily, they may be associated with fewer symptoms of infection.

DOI： 10.1016/j.ijid.2023.01.023

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PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated the anti-SARS-CoV-2 antibody levels, anti-spike (S)-immunoglobulin G (IgG) and anti-nucleocapsid (N)-IgG, and the neutralization activity of IgG antibody in COVID‑19‑convalescent plasma against variants of SARS-CoV-2, alpha, beta, gamma, delta, kappa, omicron and R.1 strains. The study included 30 patients with clinically diagnosed COVID-19. The anti-S-IgG and anti-N-IgG levels ranged from 30.0 to 555.1 and from 10.1 to 752.6, respectively. The neutralization activity (50% inhibition concentration: IC50) for the wild-type Wuhan strain ranged from < 6.3 to 81.5 µg/ml. IgG antibodies were > 100 µg/ml in 18 of 30 (60%) subjects infected with the beta variant. The IC50 values for wild-type and beta variants correlated inversely with anti-S-IgG levels (p < 0.05), but no such correlation was noted with anti-N-IgG. IgG antibodies prevented infectivity and cytopathic effects of six different variants of concern in the cell-based assays of wild-type, alpha, gamma, delta, kappa and R.1 strains, but not that of the beta and omicron strains. IgG is considered the main neutralizing activity in the blood, although other factors may be important in other body tissues.

DOI： 10.1038/s41598-023-28591-3

PubMed

担当区分：筆頭著者   記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Biochemical and Biophysical Research Communications  

Combinational antiretroviral therapy (cART) dramatically suppresses the viral load to undetectable levels in human immunodeficiency virus (HIV)-infected patients. However, HIV-1 reservoirs in CD4+T cells and myeloid cells, which can evade cART and host antiviral immune systems, are still significant obstacles to HIV-1 eradication. The “Shock and Kill” approach using latently-reversing agents (LRAs) is therefore currently developing strategies for effective HIV-1 reactivation from latency and inducing cell death. Here, we performed small-molecular chemical library screening with monocytic HIV-1 latently-infected model cells, THP-1 Nluc #225, and identified 4-phenylquinoline-8-amine (PQA) as a novel LRA candidate. PQA induced efficient HIV-1 reactivation in combination with PKC agonists including Prostratin and showed a similar tendency for HIV-1 activation in primary HIV-1 reservoirs. Furthermore, PQA induced killing of HIV-1 latently-infected cells. RNA-sequencing analysis revealed PQA had different functional mechanisms from PKC agonists, and oxidative stress-inducible genes including DDIT3 or CTSD were only involved in PQA-mediated cell death. In summary, PQA is a potential LRA lead compound that exerts novel functions related to HIV-1 activation and apoptosis-mediated cell death to eliminate HIV-1 reservoirs.

DOI： 10.1016/j.bbrc.2022.12.024

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PubMed

記述言語：日本語   出版者・発行元：Scientific Reports  

The humoral and cellular immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) upon the coronavirus disease 2019 (COVID-19) vaccination remain to be clarified. Hence, we aimed to investigate the long-term chronological changes in SARS-CoV-2 specific IgG antibody, neutralizing antibody, and T cell responses during and after receiving the BNT162b2 vaccine. We performed serological, neutralization, and T cell assays among 100 hospital workers aged 22–73 years who received the vaccine. We conducted seven surveys up to 8 months after the second vaccination dose. SARS-CoV-2 spike protein-specific IgG (IgG-S) titers and T cell responses increased significantly following the first vaccination dose. The highest titers were observed on day 29 and decreased gradually until the end of the follow-up period. There was no correlation between IgG-S and T cell responses. Notably, T cell responses were detected on day 15, earlier than the onset of neutralizing activity. This study demonstrated that both IgG-S and T cell responses were detected before acquiring sufficient levels of SARS-CoV-2 neutralizing antibodies. These immune responses are sustained for approximately 6 to 10 weeks but not for 7 months or later following the second vaccination, indicating the need for the booster dose (i.e., third vaccination).

DOI： 10.1038/s41598-022-19581-y

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PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：公益社団法人 日本薬学会  

Dihydroceramide Δ4-desaturase 1 (DEGS1) enzymatic activity is inhibited with N-(4-hydroxyphenyl)retinamide (4-HPR). We reported previously that 4-HPR suppresses severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry through a DEGS1-independent mechanism. However, it remains unclear whether DEGS1 is involved in other SARS-CoV-2 infection processes, such as virus replication and release. Here we established DEGS1 knockout (KO) in VeroE6TMPRSS2 cells. No significant difference was observed in virus production in the culture supernatant between wild-type (WT) cells and DEGS1-KO cells, although the levels of dihydroceramide (DHCer), a DEGS1 substrate, were significantly higher in DEGS1-KO cells than WT cells. Furthermore, the virus-induced cytopathic effect was also observed in DEGS1-KO cells. Importantly, the EC50 value of 4-HPR in DEGS1-KO cells was almost identical to the value reported previously in WT cells. Our results indicated the lack of involvement of DEGS1 in SARS-CoV-2 infection.

DOI： 10.1248/bpb.b22-00503

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PubMed

記述言語：英語   出版者・発行元：(公社)日本薬学会  

VeroE6/TMPRSS2細胞からジヒドロセラミドΔ4-デサチュラーゼ1(DEGS1)をノックアウトした細胞(DEGS1-KO細胞)を樹立し、SARS-CoV-2感染への影響を調べた。DEGS1の基質であるジヒドロセラミド(DHCer)のレベルは野生型(WT)よりDEGS1-KO細胞で有意に高かったが、培養上清中のウイルス産生量に有意差はなかった。DEGS1-KO細胞でもWT細胞と同様にウイルスによる細胞変性効果がみられた。ウイルス感染による細胞毒性に対する4-HPRの抑制作用のEC50値は、WT細胞とDEGS1-KO細胞の間で差がみられなかった。以上の結果から、SARS-CoV-2感染にDEGS1は関与しないと考えられた。

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BNT162b2, an mRNA-based SARS-CoV-2 vaccine (Pfizer-BioNTech, New York, NY, USA), is one of the most effective COVID-19 vaccines and has been approved by more than 130 countries worldwide. However, several studies have reported that the COVID-19 vaccine shows high interpersonal variability in terms of humoral and cellular responses, such as those with respect to SARS-CoV-2 spike protein immunoglobulin (Ig)G, IgA, IgM, neutralizing antibodies, and CD4+ and CD8+ T cells. The objective of this study is to investigate the kinetic changes in anti-SARS-CoV-2 spike IgG (IgG-S) profiles and adverse reactions and their associations with HLA profiles (HLA-A, -C, -B, -DRB1, -DQA1, -DQB1, -DPA1 and -DPB1) among 100 hospital workers from the Center Hospital of the National Center for Global Health and Medicine (NCGM), Tokyo, Japan. DQA1*03:03:01 (p = 0.017; Odd ratio (OR) 2.80, 95%confidence interval (CI) 1.05-7.25) was significantly associated with higher IgG-S production after two doses of BNT162b2, while DQB1*06:01:01:01 (p = 0.028, OR 0.27, 95%CI 0.05-0.94) was significantly associated with IgG-S declines after two doses of BNT162b2. No HLA alleles were significantly associated with either local symptoms or fever. However, C*12:02:02 (p = 0.058; OR 0.42, 95%CI 0.15-1.16), B*52:01:01 (p = 0.031; OR 0.38, 95%CI 0.14-1.03), DQA1*03:02:01 (p = 0.028; OR 0.39, 95%CI 0.15-1.00) and DPB1*02:01:02 (p = 0.024; OR 0.45, 95%CI 0.21-0.97) appeared significantly associated with protection against systemic symptoms after two doses of BNT162b2 vaccination. Further studies with larger sample sizes are clearly warranted to determine HLA allele associations with the production and long-term sustainability of IgG-S after COVID-19 vaccination.

DOI： 10.3390/vaccines10040563

PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: While increasing coverage of effective vaccines against coronavirus disease 2019 (COVID-19), emergent variants raise concerns about breakthrough infection. Data are limited, however, whether breakthrough infection during the epidemic of the variant is ascribed to insufficient vaccine-induced immunogenicity. METHODS: We described incident COVID-19 in relation to the vaccination program among workers of a referral hospital in Tokyo. During the predominantly Delta epidemic, we followed 2,415 fully vaccinated staff (BNT162b2) for breakthrough infection and selected three matched controls. We measured post-vaccination neutralizing antibodies against the wild-type, Alpha (B.1.1.7), and Delta (B.1.617.2) strains using live viruses and anti-spike antibodies using quantitative assays, and compared them using the generalized estimating equation model between the two groups. RESULTS: No COVID-19 cases occurred 1-2 months after the vaccination program during the fourth epidemic wave in Japan, dominated by the Alpha variant, while 22 cases emerged 2-4 months after the vaccination program during the fifth wave, dominated by the Delta variant. In the vaccinated cohort, all 17 cases of breakthrough infection were mild or asymptomatic and had returned to work early. There was no measurable difference between cases and controls in post-vaccination neutralizing antibody titers against the wild-type, Alpha, and Delta, and anti-spike antibody titers, while neutralizing titers against the variants were considerably lower than those against the wild-type. CONCLUSIONS: Post-vaccination neutralizing antibody titers were not decreased among patients with breakthrough infection relative to their controls under the Delta variant rampage. The result points to the importance of infection control measures in the post-vaccination era, irrespective of immunogenicity profile.

DOI： 10.1093/cid/ciab1048

PubMed

掲載種別：研究論文（学術雑誌）  

Persistence of HIV-1 latent reservoir cells during antiretroviral therapy (ART) is a major obstacle for curing HIV-1. Even though latency-reversing agents (LRAs) are under development to reactivate and eradicate latently infected cells, there are few useful models for evaluating LRA activity in vitro. Here, we establish a long-term cell culture system called the “widely distributed intact provirus elimination” (WIPE) assay. It harbors thousands of different HIV-1-infected cell clones with a wide distribution of HIV-1 provirus similar to that observed in vivo. Mathematical modeling and experimental results from this in vitro infection model demonstrates that the addition of an LRA to ART shows a latency-reversing effect and contributes to the eradication of replication-competent HIV-1. The WIPE assay can be used to optimize therapeutics against HIV-1 latency and investigate mechanistic insights into the clonal selection of heterogeneous HIV-1-infected cells.

DOI： 10.1016/j.crmeth.2021.100122

Scopus

出版者・発行元：Cold Spring Harbor Laboratory  

<bold>Background.</bold> The humoral and cellular immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) upon coronavirus disease 2019 (COVID-19) vaccination remain to be clarified. Hence, we aimed to investigate the chronological changes in SARS-CoV-2 specific IgG antibody, neutralizing antibody, and T cell responses during and after receiving the BNT162b2 vaccine.
<bold>Methods.</bold> We performed serological, neutralization, and T cell assays among 100 hospital workers aged 22-73 years who received the vaccine. We conducted five surveys on day 1, day 15, day 29 (seven days after the second dose), day 61, and days 82-96 following the first dose.
<bold>Results.</bold> SARS-CoV-2 spike protein-specific IgG (IgG-S) titers and T cell responses increased significantly following the first vaccination dose. The highest titers were observed on day 29 and decreased gradually until the end of the follow-up period. There was no correlation between IgG-S and T cell responses. Notably, T cell responses were detected on day 15, earlier than the onset of neutralizing activity.
<bold>Conclusions.</bold> This study demonstrated that both IgG-S and T cell responses were detected before acquiring sufficient levels of SARS-CoV-2 neutralizing antibodies. These early immune responses are sustained for approximately six-ten weeks following the second vaccination dose.

DOI： 10.1101/2021.11.06.21265632

出版者・発行元：Cold Spring Harbor Laboratory  

<title>Abstract</title><sec><title>Background</title>While increasing coverage of effective vaccines against coronavirus disease 2019 (COVID-19), emergent variants raise concerns about breakthrough infections. Data are limited, however, whether breakthrough infection during the epidemic of the variant is ascribed to insufficient vaccine-induced immunogenicity.

</sec><sec><title>Methods</title>We described incident COVID-19 in relation to the vaccination program among workers of a referral hospital in Tokyo. During the predominantly Delta epidemic, we followed 2,473 fully vaccinated staff (BNT162b2) for breakthrough infection and selected three matched controls. We measured pre-infection neutralizing antibodies against the wild-type, Alpha (B.1.1.7), and Delta (B.1.617.2) strains using live viruses and anti-spike antibodies using quantitative assays, and compared them using the generalized estimating equation model between the two groups.

</sec><sec><title>Results</title>No COVID-19 cases occurred 1–2 months after the vaccination program during the fourth epidemic wave in Japan, dominated by the Alpha variant, while 22 cases emerged 2–4 months after the vaccination program during the fifth wave, dominated by the Delta variant. In the vaccinated cohort, all 17 cases of breakthrough infection were mild or asymptomatic and had returned to work early. There was no measurable difference between cases and controls in pre-infection neutralizing antibody titers against the wild-type, Alpha, and Delta, and anti-spike antibody titers, while neutralizing titers against the variants were considerably lower than those against the wild-type.

</sec><sec><title>Conclusions</title>Pre-infection neutralizing antibody titers were not decreased among patients with breakthrough infection under the Delta variant rampage. The result points to the importance of infection control measures in the post-vaccination era, irrespective of immunogenicity profile.

</sec>

DOI： 10.1101/2021.10.20.21265301

記述言語：英語  

DOI： 10.1016/j.jinf.2021.05.017

PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）  

We assessed the consistency of seropositive results of three rapid immunoassays (Kits A, B, and C) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) compared to highly accurate serological tests (Abbott and Roche) among healthcare workers in a hospital in Tokyo. The seroprevalence of SARS-CoV-2 immunoglobulin G was 0.41%, 2.36%, and 0.08% using Kits A, B, and C, respectively. Of the 51 samples that were seropositive on any rapid test, all were seronegative on both the Abbott and the Roche assays. Given that the seroprevalence of SARS-CoV-2 immunoglobulin G varied widely according to the choice of rapid test and the rapid test results were inconsistent with the results of highly accurate tests, the diagnostic accuracy of rapid serological tests for SARS-CoV-2 should be assessed before introducing these tests for point-of-care testing or surveillance.

DOI： 10.35772/ghm.2021.01022

PubMed

記述言語：英語   出版者・発行元：(国研)国立国際医療研究センター  

大規模病院の医療従事者におけるSARS-CoV-2感染の血清有病率評価において、3種類の迅速ラテラルフロー・イムノアッセイ(LFIA)が2種類の高精度実験室ベース検査の結果と一致するかを調査する横断研究を実施した。迅速LFIAはキットA、キットB、キットC、高精度血清検査はAbbottおよびRocheを用いた。SARS-CoV-2免疫グロブリンGの血清有病率はキットAで0.41%、キットBで2.36%、キットCで0.08%であった。迅速検査で血清陽性であった標本51体のうち、全標本がAbbottおよびRocheアッセイの両方で血清陰性であった。SARS-CoV-2免疫グロブリンGの血清有病率は迅速検査の選択により大きく異なり、迅速検査の結果と高精度検査の結果が一致しないことから、診療現場での検査または調査に導入する前にSARS-CoV-2に対する迅速血清検査の診断精度を評価すべきであることが示された。

記述言語：英語   掲載種別：研究論文（学術雑誌）  

While there are various attempts to administer COVID-19-convalescent plasmas to SARS-CoV-2-infected patients, neither appropriate approach nor clinical utility has been established. We examined the presence and temporal changes of the neutralizing activity of IgG fractions from 43 COVID-19-convalescent plasmas using cell-based assays with multiple endpoints. IgG fractions from 27 cases (62.8%) had significant neutralizing activity and moderately to potently inhibited SARS-CoV-2 infection in cell-based assays; however, no detectable neutralizing activity was found in 16 cases (37.2%). Approximately half of the patients (~ 41%), who had significant neutralizing activity, lost the neutralization activity within ~ 1 month. Despite the rapid decline of neutralizing activity in plasmas, good amounts of SARS-CoV-2-S1-binding antibodies were persistently seen. The longer exposure of COVID-19 patients to greater amounts of SARS-CoV-2 elicits potent immune response to SARS-CoV-2, producing greater neutralization activity and SARS-CoV-2-S1-binding antibody amounts. The dilution of highly-neutralizing plasmas with poorly-neutralizing plasmas relatively readily reduced neutralizing activity. The presence of good amounts of SARS-CoV-2-S1-binding antibodies does not serve as a surrogate ensuring the presence of good neutralizing activity. In selecting good COVID-19-convalescent plasmas, quantification of neutralizing activity in each plasma sample before collection and use is required.

DOI： 10.1038/s41598-021-84733-5

PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The quantitative range and reproducibility of current serological tests for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are not optimized. Herein, we developed a diagnostic test that detects SARS-CoV-2 IgG and IgM with high quantitativeness and reproducibility and low interference. The system was based on the high-sensitivity chemiluminescence enzyme immunoassay (HISCL) platform and detects IgG and IgM specific to SARS-CoV-2 spike and nucleocapsid proteins. Quantification accuracy and reproducibility were evaluated using serially diluted samples from 60 SARS-CoV-2-infected patients. Assay performance was evaluated using serum samples from the SARS-CoV-2-infected patients and 500 SARS-CoV-2-negative serum samples collected before the emergence of SARS-CoV-2. The system showed high quantification accuracy (range, 102), high reproducibility (within 5%), and no cross-reaction between SARS1- and MERS-S proteins. Detection accuracy was 98.3% and 93.3% for IgG and IgM against spike proteins and 100% and 71.7% for IgG and IgM against nucleocapsid proteins, respectively. Mean antibody levels were > 10 times that in negative samples upon admission and > 100 times that at convalescent periods. Clinical severity upon admission was not correlated with IgG or IgM levels. This highly quantitative, reproducible assay system with high clinical performance may help analyze temporal serological/immunological profiles of SARS-CoV-2 infection and SARS-CoV-2 vaccine effectiveness.

DOI： 10.1038/s41598-021-84387-3

PubMed

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

Advances in antiviral therapy have dramatically improved the therapeutic effects on HIV type 1 (HIV-1) infection. However, even with potent combined antiretroviral therapy, HIV-1 latently infected cells cannot be fully eradicated. Latency-reversing agents (LRAs) are considered a potential tool for eliminating such cells; however, recent in vitro and in vivo studies have raised serious concerns regarding the efficacy and safety of the "shock and kill" strategy using LRAs. In the present study, we examined the activity and safety of a panel of protein kinase C (PKC) activators with a diacylglycerol (DAG)-lactone structure that mimics DAG, an endogenous ligand for PKC isozymes. YSE028, a DAG-lactone derivative, reversed HIV-1 latency in vitro when tested using HIV-1 latently infected cells (e.g., ACH2 and J-Lat cells) and primary cells from HIV-1-infected individuals. The activity of YSE028 in reversing HIV-1 latency was synergistically enhanced when combined with JQ1, a bromodomain and extra-terminal inhibitor LRA. DAG-lactone PKC activators also induced caspase-mediated apoptosis, specifically in HIV-1 latently infected cells. In addition, these DAG-lactone PKC activators showed minimal toxicity in vitro and in vivo. These data suggest that DAG-lactone PKC activators may serve as potential candidates for combination therapy against HIV-1 latently infected cells, especially when combined with other LRAs with a different mechanism, to minimize side effects and achieve maximum efficacy in various reservoir cells of the whole body.

DOI： 10.3389/fmicb.2021.636276

PubMed

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：英語  

記述言語：日本語