Human immunodeficiency virus (HIV) preferentially infects T-lymphocytes by integrating into host DNA and forming a latent transcriptionally silent provirus. As previously shown, HIV-1 alters migration modes of T-lymphocytes by co-regulating viral gene expression with human C-X-C chemokine receptor-4 (CXCR4). Here, we show that motility of infected T-lymphocytes is cell size dependent. In cell migration assays, migrating cells are consistently larger than non-migrating cells. This effect is drug-treatment independent. The cell size dependent motility observed in a previously generated Jurkat latency model correlates with the motility of primary human CD4+ T-cells containing a modified HIV-1 full-length construct JLatd2GFP. In addition, large migrating T-cells, latently infected with HIV, show a slightly decreased rate of reactivation from latency. these results demonstrate that HIV reactivation is cell migration-dependent, where host cell size acts as a catalyst for altered migration velocity. We believe that host cell size controlled migration uncovers an additional mechanism of cellular controlled viral fate determination important for virus dissemination and reactivation from latency. This observation may provide more insights into viral-host interactions regulating cell migration and reactivation from latency and helps in the design and implementation of novel therapeutic strategies.
{"title":"Cell size dependent migration of T-cells latently infected with HIV.","authors":"Kathrin Bohn-Wippert, Roy D Dar","doi":"10.36069/JoLS/20200301","DOIUrl":"https://doi.org/10.36069/JoLS/20200301","url":null,"abstract":"<p><p>Human immunodeficiency virus (HIV) preferentially infects T-lymphocytes by integrating into host DNA and forming a latent transcriptionally silent provirus. As previously shown, HIV-1 alters migration modes of T-lymphocytes by co-regulating viral gene expression with human C-X-C chemokine receptor-4 (CXCR4). Here, we show that motility of infected T-lymphocytes is cell size dependent. In cell migration assays, migrating cells are consistently larger than non-migrating cells. This effect is drug-treatment independent. The cell size dependent motility observed in a previously generated Jurkat latency model correlates with the motility of primary human CD4+ T-cells containing a modified HIV-1 full-length construct JLatd2GFP. In addition, large migrating T-cells, latently infected with HIV, show a slightly decreased rate of reactivation from latency. these results demonstrate that HIV reactivation is cell migration-dependent, where host cell size acts as a catalyst for altered migration velocity. We believe that host cell size controlled migration uncovers an additional mechanism of cellular controlled viral fate determination important for virus dissemination and reactivation from latency. This observation may provide more insights into viral-host interactions regulating cell migration and reactivation from latency and helps in the design and implementation of novel therapeutic strategies.</p>","PeriodicalId":87302,"journal":{"name":"Journal of life sciences (Westlake Village, Calif.)","volume":"2 1","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2020-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7250449/pdf/nihms-1581275.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37979686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Breast cancer classifications are based on the presence or absence of estrogen receptor and progesterone receptor along with the overexpression or amplification of the Her2 receptor. Although the overall 5-year survival rate of breast cancer patients has increased due to the use of targeted therapies, a subset of patients can acquire resistance over time or are unresponsive when presented in the clinic. Novel therapies focusing on molecular pathways and cell cycle regulation currently being used in the clinic may lead to increased response in this subset of patients.
{"title":"Regulation and New Treatment Strategies in Breast Cancer.","authors":"Rosa-Maria Ferraiuolo, Kay-Uwe Wagner","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Breast cancer classifications are based on the presence or absence of estrogen receptor and progesterone receptor along with the overexpression or amplification of the Her2 receptor. Although the overall 5-year survival rate of breast cancer patients has increased due to the use of targeted therapies, a subset of patients can acquire resistance over time or are unresponsive when presented in the clinic. Novel therapies focusing on molecular pathways and cell cycle regulation currently being used in the clinic may lead to increased response in this subset of patients.</p>","PeriodicalId":87302,"journal":{"name":"Journal of life sciences (Westlake Village, Calif.)","volume":"1 3","pages":"23-38"},"PeriodicalIF":0.0,"publicationDate":"2019-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7039658/pdf/nihms-1069247.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37675283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Editorial: Vaccine Hesitancy","authors":"M. Linterman","doi":"10.36069/jols/20191201","DOIUrl":"https://doi.org/10.36069/jols/20191201","url":null,"abstract":"","PeriodicalId":87302,"journal":{"name":"Journal of life sciences (Westlake Village, Calif.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45200334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Combining immune checkpoint blockade with ErbB targeted therapies for cancer treatment","authors":"Zhida Liu, Chuanhui Han, yang-xin fu","doi":"10.36069/jols/20191202","DOIUrl":"https://doi.org/10.36069/jols/20191202","url":null,"abstract":"","PeriodicalId":87302,"journal":{"name":"Journal of life sciences (Westlake Village, Calif.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44338145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mitochondria fulfill the high metabolic energy demands of the kidney and are regularly exposed to oxidative stress causing mitochondrial damage. The selective removal of damaged and dysfunctional mitochondria through a process known as mitophagy is essential in maintaining cellular homeostasis and physiological function. Mitochondrial quality control by mitophagy is particularly crucial for an organ such as the kidney, which is rich in mitochondria. The role of mitophagy in the pathogenesis of kidney diseases has lately gained significant attention. In this review, we summarize the current understanding of the implications of mitophagy during pathological conditions of the kidney, including acute and chronic kidney diseases.
{"title":"The Emerging Role of Mitophagy in Kidney Diseases.","authors":"Divya Bhatia, Mary E Choi","doi":"10.36069/jols/20191203","DOIUrl":"https://doi.org/10.36069/jols/20191203","url":null,"abstract":"<p><p>Mitochondria fulfill the high metabolic energy demands of the kidney and are regularly exposed to oxidative stress causing mitochondrial damage. The selective removal of damaged and dysfunctional mitochondria through a process known as mitophagy is essential in maintaining cellular homeostasis and physiological function. Mitochondrial quality control by mitophagy is particularly crucial for an organ such as the kidney, which is rich in mitochondria. The role of mitophagy in the pathogenesis of kidney diseases has lately gained significant attention. In this review, we summarize the current understanding of the implications of mitophagy during pathological conditions of the kidney, including acute and chronic kidney diseases.</p>","PeriodicalId":87302,"journal":{"name":"Journal of life sciences (Westlake Village, Calif.)","volume":"1 3","pages":"13-22"},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041910/pdf/nihms-1069240.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37678498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Metabolic adaptations to glutamine deprivation in pancreatic cancer","authors":"Ying Yang, M. Gabra, Mei Kong","doi":"10.36069/jols/20190903","DOIUrl":"https://doi.org/10.36069/jols/20190903","url":null,"abstract":"","PeriodicalId":87302,"journal":{"name":"Journal of life sciences (Westlake Village, Calif.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45916985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The human genome is exposed to a gamut of cellular and exogenous insults on a daily basis which needs to be monitored for proper cellular functioning and survival. This surveillance is undertaken by a myriad of protein players that ensure temporal and spatial regulation of cellular homeostasis. Kinases lie at the epicenter of the DNA damage response and exhibit a dynamic functionality, from responding to the damage to regulating the role of other proteins involved in detecting and repairing the damage. Here, we review some of the key kinases involved in DNA damage response pathways and their inhibitors that are either in clinical trials or have received approval for disease treatment.
{"title":"Kinases: The \"Indispensables\"of the DNA Damage Response Cascade","authors":"V. Menon, M. M. Dcona","doi":"10.36069/jols/20190902","DOIUrl":"https://doi.org/10.36069/jols/20190902","url":null,"abstract":"The human genome is exposed to a gamut of cellular and exogenous insults on a daily basis which needs to be monitored for proper cellular functioning and survival. This surveillance is undertaken by a myriad of protein players that ensure temporal and spatial regulation of cellular homeostasis. Kinases lie at the epicenter of the DNA damage response and exhibit a dynamic functionality, from responding to the damage to regulating the role of other proteins involved in detecting and repairing the damage. Here, we review some of the key kinases involved in DNA damage response pathways and their inhibitors that are either in clinical trials or have received approval for disease treatment.","PeriodicalId":87302,"journal":{"name":"Journal of life sciences (Westlake Village, Calif.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49077501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Around 37 million people are living with HIV worldwide, with a million deaths due to HIV in 2017. While only ~60% of the infected population are receiving antiretroviral therapy (ART), by taking a combination of drugs suppressing different stage of the HIV lifecycle to lower the viral burden. While the treatment is very effective it does not eliminate HIV from the patient’s body and non-AIDS comorbidities (cardiovascular diseases and cancers) and unrelenting rate of new infections (around 2 million infections per year) have become a major concern and, thus new approaches are needed that no longer continuously suppress HIV but actually cure people.
{"title":"Road to HIV cure; from Berlin to London and beyond","authors":"T. Broek","doi":"10.36069/JOLS/20190602","DOIUrl":"https://doi.org/10.36069/JOLS/20190602","url":null,"abstract":"Around 37 million people are living with HIV worldwide, with a million deaths due to HIV in 2017. While only ~60% of the infected population are receiving antiretroviral therapy (ART), by taking a combination of drugs suppressing different stage of the HIV lifecycle to lower the viral burden. While the treatment is very effective it does not eliminate HIV from the patient’s body and non-AIDS comorbidities (cardiovascular diseases and cancers) and unrelenting rate of new infections (around 2 million infections per year) have become a major concern and, thus new approaches are needed that no longer continuously suppress HIV but actually cure people.","PeriodicalId":87302,"journal":{"name":"Journal of life sciences (Westlake Village, Calif.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49357969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"How daily habits help you deal with stress","authors":"D. Lith","doi":"10.36069/JOLS/20190606","DOIUrl":"https://doi.org/10.36069/JOLS/20190606","url":null,"abstract":"","PeriodicalId":87302,"journal":{"name":"Journal of life sciences (Westlake Village, Calif.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46396138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The human immunodeficiency virus (HIV) infection of the immune cells expressing the cluster of differentiation 4 cell surface glycoprotein (CD4+ cells) causes progressive decline of the immune system and leads to the acquired immunodeficiency syndrome (AIDS). The ongoing global HIV/AIDS pandemic has already claimed over 35 million lives. Even after 37 years into the epidemic, neither a cure is available for the 37 million people living with HIV (PLHIV) nor is a vaccine discovered to avert the millions of new HIV infections that continue to occur each year. If left untreated, HIV infection typically progresses to AIDS and, ultimately, causes death in a majority of PLHIV. The recommended combination antiretroviral therapy (cART) suppresses virus replication and viremia, prevents or delays progression to AIDS, reduces transmission rates, and lowers HIV-associated mortality and morbidity. However, because cART does not eliminate HIV, and an enduring pool of infected resting memory CD4+ T cells (latent HIV reservoir) is established early on, any interruption to cART leads to a relapse of viremia and disease progression. Hence, strict adherence to a life-long cART regimen is mandatory for managing HIV infection in PLHIV. The HIV-1-specific cytotoxic T cells expressing the CD8 glycoprotein (CD8+ CTL) limit the virus replication in vivo by recognizing the viral antigens presented by human leukocyte antigen (HLA) class I molecules on the infected cell surface and killing those cells. Nevertheless, CTLs fail to durably control HIV-1 replication and disease progression in the absence of cART. Intriguingly, <1% of cART-naive HIV-infected individuals called elite controllers/HIV controllers (HCs) exhibit the core features that define a HIV-1 "functional cure" outcome in the absence of cART: durable viral suppression to below the limit of detection, long-term non-progression to AIDS, and absence of viral transmission. Robust HIV-1-specific CTL responses and prevalence of protective HLA alleles associated with enduring HIV-1 control have been linked to the HC phenotype. An understanding of the molecular mechanisms underlying the CTL-mediated suppression of HIV-1 replication and disease progression in HCs carrying specific protective HLA alleles may yield promising insights towards advancing the research on HIV cure and prophylactic HIV vaccine.
人类免疫缺陷病毒(HIV)感染了表达分化 4 簇细胞表面糖蛋白的免疫细胞(CD4+细胞),导致免疫系统逐渐衰退,引发获得性免疫缺陷综合症(艾滋病)。全球艾滋病毒/艾滋病的持续流行已经夺走了 3500 多万人的生命。即使在疫情流行 37 年后的今天,3,700 万艾滋病病毒感染者(PLHIV)仍无法治愈,也没有发现疫苗来避免每年新增的数百万艾滋病病毒感染者。如果不及时治疗,艾滋病毒感染通常会发展为艾滋病,并最终导致大多数艾滋病毒感染者死亡。推荐的抗逆转录病毒联合疗法(cART)可抑制病毒复制和病毒血症,预防或延缓艾滋病的发展,降低传播率,并降低与艾滋病毒相关的死亡率和发病率。然而,由于 cART 并不能消除 HIV,而且受感染的静息记忆 CD4+ T 细胞(潜伏 HIV 储库)很早就已建立,因此任何 cART 中断都会导致病毒血症复发和疾病进展。因此,要控制艾滋病毒感染,PLHIV 必须严格遵守终生 cART 方案。表达 CD8 糖蛋白的 HIV-1 特异性细胞毒性 T 细胞(CD8+ CTL)通过识别感染细胞表面由人类白细胞抗原(HLA)I 类分子呈现的病毒抗原并杀死这些细胞,从而限制病毒在体内的复制。然而,在没有 cART 的情况下,CTL 无法持久地控制 HIV-1 复制和疾病进展。耐人寻味的是,HIV 控制者(HCs)表现出了在没有 cART 的情况下定义 HIV-1 "功能性治愈 "结果的核心特征:持久的病毒抑制至检测限以下、长期不发展为艾滋病以及没有病毒传播。强大的 HIV-1 特异性 CTL 反应和与持久控制 HIV-1 相关的保护性 HLA 等位基因的流行与 HC 表型有关。了解携带特异性保护性 HLA 等位基因的 HC 中 CTL 介导的抑制 HIV-1 复制和疾病进展的分子机制,可能会为推进 HIV 治愈和预防性 HIV 疫苗的研究提供有前景的见解。
{"title":"Immune Control of HIV.","authors":"Muthukumar Balasubramaniam, Jui Pandhare, Chandravanu Dash","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The <b>h</b>uman <b>i</b>mmunodeficiency <b>v</b>irus (HIV) infection of the immune cells expressing the <b>c</b>luster of <b>d</b>ifferentiation <b>4</b> cell surface glycoprotein (CD4<sup>+</sup> cells) causes progressive decline of the immune system and leads to the <b>a</b>cquired <b>i</b>mmuno<b>d</b>eficiency <b>s</b>yndrome (AIDS). The ongoing global HIV/AIDS pandemic has already claimed over 35 million lives. Even after 37 years into the epidemic, neither a cure is available for the 37 million <b>p</b>eople <b>l</b>iving with <b>HIV</b> (PLHIV) nor is a vaccine discovered to avert the millions of new HIV infections that continue to occur each year. If left untreated, HIV infection typically progresses to AIDS and, ultimately, causes death in a majority of PLHIV. The recommended <b>c</b>ombination <b>a</b>nti<b>r</b>etroviral <b>t</b>herapy (cART) suppresses virus replication and viremia, prevents or delays progression to AIDS, reduces transmission rates, and lowers HIV-associated mortality and morbidity. However, because cART does not eliminate HIV, and an enduring pool of infected resting memory CD4<sup>+</sup> T cells (latent HIV reservoir) is established early on, any interruption to cART leads to a relapse of viremia and disease progression. Hence, strict adherence to a life-long cART regimen is mandatory for managing HIV infection in PLHIV. The HIV-1-specific <b>c</b>yto<b>t</b>oxic <b>T</b> cells expressing the CD8 glycoprotein (CD8<sup>+</sup> CTL) limit the virus replication <i>in vivo</i> by recognizing the viral antigens presented by <b>h</b>uman <b>l</b>eukocyte <b>a</b>ntigen (HLA) class I molecules on the infected cell surface and killing those cells. Nevertheless, CTLs fail to durably control HIV-1 replication and disease progression in the absence of cART. Intriguingly, <1% of cART-naive HIV-infected individuals called elite controllers/<b>H</b>IV <b>c</b>ontrollers (HCs) exhibit the core features that define a HIV-1 \"functional cure\" outcome in the absence of cART: durable viral suppression to below the limit of detection, long-term non-progression to AIDS, and absence of viral transmission. Robust HIV-1-specific CTL responses and prevalence of protective HLA alleles associated with enduring HIV-1 control have been linked to the HC phenotype. An understanding of the molecular mechanisms underlying the CTL-mediated suppression of HIV-1 replication and disease progression in HCs carrying specific protective HLA alleles may yield promising insights towards advancing the research on HIV cure and prophylactic HIV vaccine.</p>","PeriodicalId":87302,"journal":{"name":"Journal of life sciences (Westlake Village, Calif.)","volume":"1 1","pages":"4-37"},"PeriodicalIF":0.0,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6714987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141285570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}