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Therapeutic modalities designed specifically to inhibit COVID-19 infection and replication would limit progressive COVID-19-associated pulmonary disease in infected patients and prevent or limit systemic disease. If effective, antivirals could reduce viral transmission rates by reducing viral burden and allow time for immune clearance. For individuals infected with acute-stage disease, antivirals in support of the existing vaccines could reduce COVID-19 hospitalizations and deaths. Here, we evaluate MRCV-19, a phosphorodiamidate morpholino oligo with delivery dendrimer (Vivo-Morpholino), to prevent coronavirus infection in a cell culture model. This is a novel antiviral that effectively inhibits SARS-CoV-2 replication in vitro. By design, MRCV-19 targets the SARS-CoV-2 5’UTR and overlaps the pp1a start site of translation in order to block access of the translation initiation complex to the start. MRCV-19 testing is conducted in a high-throughput, 384-well plate format with a 10-point dose-response curve (common ratio of 2) assayed in duplicate with parallel cytotoxicity evaluations. MRCV-19 was shown to be more effective than hydroxychloroquine and remdesivir in our CPE reduction assay with low toxicity. The clinical translational impact of this study is providing the basis for evaluating MRCV-19 on a large scale in an appropriate infection model for toxicity and systemic high-level inhibition of SARS-CoV-2, which could lead in time to phase I testing in humans.
James E. K. Hildreth; Jon D. Moulton; Donald J. Alcendor. Vivo-Morpholino-Based Antiviral for SARS-CoV-2: Implications for Novel Therapies in the Treatment of Acute COVID-19 Disease. Biomedicines 2021, 9, 1018 .
AMA StyleJames E. K. Hildreth, Jon D. Moulton, Donald J. Alcendor. Vivo-Morpholino-Based Antiviral for SARS-CoV-2: Implications for Novel Therapies in the Treatment of Acute COVID-19 Disease. Biomedicines. 2021; 9 (8):1018.
Chicago/Turabian StyleJames E. K. Hildreth; Jon D. Moulton; Donald J. Alcendor. 2021. "Vivo-Morpholino-Based Antiviral for SARS-CoV-2: Implications for Novel Therapies in the Treatment of Acute COVID-19 Disease." Biomedicines 9, no. 8: 1018.
There has been a continuous underrepresentation of minorities in healthcare research and vaccine trials, along with long-standing systemic racism and discrimination that have been fueling the distrust of the healthcare system among these communities for decades. The history and legacy of racial injustices and negative experiences within a culturally insensitive healthcare system have greatly contributed to vaccine hesitancy among ethnic minorities. COVID-19 vaccine hesitancy will impact vaccine uptake in the US, subsequently hindering the establishment of herd immunity (75–85% of the population vaccinated) to mitigate SARS-CoV-2 infection and transmission. Information targeting underserved racial/ethnic minorities in the US in a culturally competent manner has been lacking. This information is crucial for educating these communities about COVID-19 vaccines and their distribution as well as dispelling misinformation regarding vaccine trials, safety, and efficacy. This lack of education has greatly contributed to COVID-19 vaccine hesitancy and will increase disparities in vaccine uptake. Moreover, timely vaccinations are also essential to curtailing virus transmission and the emergence of SARS-CoV-2 variants that may evade the immune response produced by the three existing COVID-19 vaccines.
James Hildreth; Donald Alcendor. Targeting COVID-19 Vaccine Hesitancy in Minority Populations in the US: Implications for Herd Immunity. Vaccines 2021, 9, 489 .
AMA StyleJames Hildreth, Donald Alcendor. Targeting COVID-19 Vaccine Hesitancy in Minority Populations in the US: Implications for Herd Immunity. Vaccines. 2021; 9 (5):489.
Chicago/Turabian StyleJames Hildreth; Donald Alcendor. 2021. "Targeting COVID-19 Vaccine Hesitancy in Minority Populations in the US: Implications for Herd Immunity." Vaccines 9, no. 5: 489.
Human cytomegalovirus (HCMV) is a member of Betaherpesvirus family and is the leading infectious cause of neurosensory hearing loss, vision loss and neurocognitive disability among congenitally infected children. HCMV is a ubiquitous central nervous system (CNS) pathogen that causes significant morbidity and mortality in individuals that are immune compromised. Even more, HCMV is an important opportunistic pathogen that can cause life threatening disease in HIV patients and transplant recipients. HCMV has broad tropism for multiple cell types including cells of the vascular barrier systems. My aim is to explore HCMV infectivity in human vascular pericyte populations with implications for its role in human vascular diseases. Human primary low passaged pericyte populations were examined for HCMV infectivity along with controls by means of phase microscopy, immunofluorescence, immunohistochemistry, electron microscopy, real-time reverse-transcription polymerase chain reaction (RT-PCR), and quantitative RT-PCR (qRT-PCR), the proinflammatory cytokines assay, and HCMV-GFP recombinant virus. I have discovered that human vascular pericytes from multiple barrier systems that includes the blood brain barrier (BBB), inner blood retinal barrier (IRRB), glomerular barrier, and pericytes of vascular systems of the placenta, and adipose tissue are fully permissive for HCMV lytic replication. I also observed consistent induction of proinflammatory and angiogenic cytokines after HCMV infection in all of these pericyte populations. Even more, I have examined murine retinal pericyte and found that they are also permissive for mouse cytomegalovirus (MCMV) lytic replication. The mechanisms associated with HCMV infection and the increased risks for the development of vascular diseases requires further investigation. Studies have shown that people exposed to HCMV infection had higher risk for vascular disease. There are antivirals that can effectively inhibit HCMV replication thus therapeutic modalities designed to specifically protect pericytes populations from HCMV infection could impact vascular disease outcomes especially among the elderly and immune compromise patients.
Donald J. Alcendor. Effects of Cytomegalovirus on Pericytes. Stem Cell Biology and Regenerative Medicine 2021, 99 -124.
AMA StyleDonald J. Alcendor. Effects of Cytomegalovirus on Pericytes. Stem Cell Biology and Regenerative Medicine. 2021; ():99-124.
Chicago/Turabian StyleDonald J. Alcendor. 2021. "Effects of Cytomegalovirus on Pericytes." Stem Cell Biology and Regenerative Medicine , no. : 99-124.
The JC polyomavirus (JCPyV/JCV) is a member of the Polyomaviridae family and is ubiquitious in the general population, infecting 50–80% of individuals globally. A primary infection with JCV usally results in an asymptomatic, persistent infection that establishes latency in the renourinary tract. Reactivation from latency via iatrogenic immununosuppression for allograft transplantation may result in organ pathology and a potential life-threatening neuropathological disease in the form of progressive multifocal leukoencephalopathy (PML). Currently, no treatment exists for PML, a rare complication that occurs after transplantation, with an incidence of 1.24 per 1000 persons a year among solid organ transplant patients. PML is also observed in HIV patients who are immununosuppressed and are not receiving antiretroviral therapy, as well as individuals treated with biologics to suppress chronic inflammatory responses due to multiple sclerosis, Crohn’s disease, non-Hodgkin’s lymphoma, rheumatoid arthritis, and other autoimmune-mediated hematological disorders. Here, we describe the proposed mechanisms of JCV reactivation as it relates to iatrogenic immunosuppression for graft survival and the treatment of proinflammatory disease, such as biologics, proposed trafficking of JCV from the renourinary tract, JCV central nervous system dissemination and the pathology of PML in immunosuppressed patients, and potential novel therapeutics for PML disease.
James Hildreth; Donald Alcendor. JC Polyomavirus and Transplantation: Implications for Virus Reactivation after Immunosuppression in Transplant Patients and the Occurrence of PML Disease. Transplantology 2021, 2, 37 -48.
AMA StyleJames Hildreth, Donald Alcendor. JC Polyomavirus and Transplantation: Implications for Virus Reactivation after Immunosuppression in Transplant Patients and the Occurrence of PML Disease. Transplantology. 2021; 2 (1):37-48.
Chicago/Turabian StyleJames Hildreth; Donald Alcendor. 2021. "JC Polyomavirus and Transplantation: Implications for Virus Reactivation after Immunosuppression in Transplant Patients and the Occurrence of PML Disease." Transplantology 2, no. 1: 37-48.
Isolation of cytotrophoblasts from primary placental tissue may be costly and time consuming with variable results. In this paper, we provide a simple, affordable, and efficient method that may performed using common laboratory supplies to achieve consistent in vitro isolation of cytotrophoblasts from villous tissue. Trophoblast populations are identified based on morphology and phenotyping, which employs the timely extraction of villous nodes from the placenta prior to cultivation and isolation of nodal outgrowth by visual guidance for selective capture of cytotrophoblast populations and subculture. This method allows for the isolation of cytotrophoblasts free of contamination with other placental cell types. Isolated cells stain positive for the specific cytotrophoblast biomarker cytokeratin 7 and Human Chorionic Gonadotropin (HCG). Subcultured cells grow to confluency to establish monolayers that may be passaged in culture and later used to develop primary syncytiotrophoblasts over time. These primary cytotrophoblast populations may be employed using in in vitro placenta-on-a chip models to better understand placental cell biology and function, as well as physiological responses after exposure to toxicants, and infectious agents. This technique may be modified for selective isolation of specific cell types within different tissues from multiple organ systems.
Ashley Serjilus; Donald J Alcendor. Unique method for human villous trophoblasts isolation from placental tissue explants. 2020, 6, 1 .
AMA StyleAshley Serjilus, Donald J Alcendor. Unique method for human villous trophoblasts isolation from placental tissue explants. . 2020; 6 (6):1.
Chicago/Turabian StyleAshley Serjilus; Donald J Alcendor. 2020. "Unique method for human villous trophoblasts isolation from placental tissue explants." 6, no. 6: 1.
Alzheimer’s disease (AD) and related dementias disproportionately impact racial and ethnic minorities. The racial and ethnic disparities in AD could be explained by differences in cerebral vascular disease pathology. Endothelin-1 (ET-1) is a potent vasoconstrictive peptide that regulates smooth muscle, endothelial cell, and pericyte contractions that may result in cerebral vascular constriction, leading to cerebral hypoperfusion; over time, ET-1 may result in neuronal injury contributing to the pathology of AD. Upregulation of the ET-1 system has been observed in African Americans when compared with non-Hispanic Whites. The role of the ET-1 system as a driver of ethnic disparities in AD requires further investigation. Targeting of the ET-1 system as a therapeutic intervention that could impact AD progression also needs further study. Dysregulation of ET-1 in Hispanic/Latino populations largely have been unexplored. Genetics linking ET-1 dysregulation and racial disparities in AD also needs further investigation. In this review, I examine how AD effects underserved minority populations and how dysregulation of the ET-1 system specifically predisposes ethnic minorities to AD. In addition, I examine the molecular interactions of the ET-1 system and amyloid beta, the role the ET-1 system in neurodegeneration, potential therapeutics for ET-1 dysregulation, and the impact on AD progression.
Donald Alcendor. Dysregulation of Endothelin-1: Implications for Health Disparities in Alzheimer’s Disease. Journal of Personalized Medicine 2020, 10, 199 .
AMA StyleDonald Alcendor. Dysregulation of Endothelin-1: Implications for Health Disparities in Alzheimer’s Disease. Journal of Personalized Medicine. 2020; 10 (4):199.
Chicago/Turabian StyleDonald Alcendor. 2020. "Dysregulation of Endothelin-1: Implications for Health Disparities in Alzheimer’s Disease." Journal of Personalized Medicine 10, no. 4: 199.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a betacoronavirus that causes the novel coronavirus disease 2019 (COVID-19), is highly transmissible and pathogenic for humans and may cause life-threatening disease and mortality, especially in individuals with underlying comorbidities. First identified in an outbreak in Wuhan, China, COVID-19 is affecting more than 185 countries and territories around the world, with more than 15,754,651 confirmed cases and more than 640,029 deaths. Since December 2019, SARS-CoV-2 transmission has become a global threat, which includes confirmed cases in all 50 states within the United States (US). As of 25 July 2020, the Johns Hopkins Whiting School of Engineering Center for Systems Science and Engineering reports more than 4,112,651 cases and 145,546 deaths. To date, health disparities are associated with COVID-19 mortality among underserved populations. Here, the author explores potential underlying reasons for reported disproportionate, increased risks of mortality among African Americans and Hispanics/Latinos with COVID-19 compared with non-Hispanic Whites. The author examines the underlying clinical implications that may predispose minority populations and the adverse clinical outcomes that may contribute to increased risk of mortality. Government and community-based strategies to safeguard minority populations at risk for increased morbidity and mortality are essential. Underserved populations living in poverty with limited access to social services across the US are more likely to have underlying medical conditions and are among the most vulnerable. Societal and cultural barriers for ethnic minorities to achieve health equity are systemic issues that may be addressed only through shifts in governmental policies, producing long-overdue, substantive changes to end health care inequities.
Donald J. Alcendor. Racial Disparities-Associated COVID-19 Mortality among Minority Populations in the US. Journal of Clinical Medicine 2020, 9, 2442 .
AMA StyleDonald J. Alcendor. Racial Disparities-Associated COVID-19 Mortality among Minority Populations in the US. Journal of Clinical Medicine. 2020; 9 (8):2442.
Chicago/Turabian StyleDonald J. Alcendor. 2020. "Racial Disparities-Associated COVID-19 Mortality among Minority Populations in the US." Journal of Clinical Medicine 9, no. 8: 2442.
Alzheimer’s disease (AD) is a progressive neurodegenerative disease that is the most common cause of dementia, especially among aging populations. Despite advances in AD research, the underlying cause and the discovery of disease-modifying treatments have remained elusive. Two key features of AD pathology are the aberrant deposition of amyloid beta (amyloid-β or Aβ) proteins in the brain parenchyma and Aβ toxicity in brain pericytes of the neurovascular unit/blood–brain barrier (NVU/BBB). This toxicity induces oxidative stress in pericytes and leads to capillary constriction. The interaction between pericytes and Aβ proteins results in the release of endothelin-1 in the pericytes. Endothelin-1 interacts with ETA receptors to cause pericyte contraction. This pericyte-mediated constriction of brain capillaries can cause chronic hypoperfusion of the brain microvasculature, subsequently leading to the neurodegeneration and cognitive decline observed in AD patients. The interaction between Aβ proteins and brain pericytes is largely unknown and requires further investigation. This review provides an updated overview of the interaction between Aβ proteins with pericytes, one the most significant and often forgotten cellular components of the BBB and the inner blood–retinal barrier (IBRB). The IBRB has been shown to be a window into the central nervous system (CNS) that could allow the early diagnosis of AD pathology in the brain and the BBB using modern photonic imaging systems such as optical coherence tomography (OCT) and two-photon microscopy. In this review, I explore the regulation of Aβ proteins in the brain parenchyma, their role in AD pathobiology, and their association with pericyte function. This review discusses Aβ proteins and pericytes in the ocular compartment of AD patients as well as strategies to rescue or protect pericytes from the effects of Aβ proteins, or to replace them with healthy cells.
Donald J. Alcendor. Interactions between Amyloid-Β Proteins and Human Brain Pericytes: Implications for the Pathobiology of Alzheimer’s Disease. Journal of Clinical Medicine 2020, 9, 1490 .
AMA StyleDonald J. Alcendor. Interactions between Amyloid-Β Proteins and Human Brain Pericytes: Implications for the Pathobiology of Alzheimer’s Disease. Journal of Clinical Medicine. 2020; 9 (5):1490.
Chicago/Turabian StyleDonald J. Alcendor. 2020. "Interactions between Amyloid-Β Proteins and Human Brain Pericytes: Implications for the Pathobiology of Alzheimer’s Disease." Journal of Clinical Medicine 9, no. 5: 1490.
BK polyomavirus (BKPyV), or BKV infection, is ubiquitous and usually non-pathogenic, with subclinical infections in 80-90% of adults worldwide. BKV infection is often associated with pathology in immunocompromised individuals. BKV infection often is associated with renal impairment, including ureteral stenosis, hemorrhagic cystitis, and nephropathy. BKV infection is less commonly associated with pneumonitis, retinitis, liver disease, and meningoencephalitis. BKV is known to replicate, establish latency, undergo reactivation, and induce clinical pathology in renal tubular epithelial cells. However, recent in vitro studies support the notion that BKV has expanded tropism-targeting glomerular parenchymal cells of the human kidney, which could impact glomerular function, enhance inflammation, and serve as viral reservoirs for reactivation from latency during immunosuppression. The implications of BKV expanded tropism in the glomerulus, and how specific host and viral factors that would contribute to glomerular inflammation, cytolysis, and renal fibrosis are related to BKV associated nephropathy (BKVAN), have not been explored. The pathogenesis of BKV in human glomerular parenchymal cells is poorly understood. In this review, I examine target cell populations for BKV infectivity in the human glomerulus. Specifically, I explore the implications of BKV expanded tropism in the glomerulus with regard viral entry, replication, and dissemination via cell types exposed to BKV trafficking in glomerulus. I also describe cellular targets shown to be permissive in vitro and in vivo for BKV infection and lytic replication, the potential role that glomerular parenchymal cells play in BKV latency and/or reactivation after immunosuppression, and the rare occurrence of BKV pathology in glomerular parenchymal cells in patients with BKVAN.
Donald J. Alcendor. BK Polyomavirus Virus Glomerular Tropism: Implications for Virus Reactivation from Latency and Amplification during Immunosuppression. Journal of Clinical Medicine 2019, 8, 1477 .
AMA StyleDonald J. Alcendor. BK Polyomavirus Virus Glomerular Tropism: Implications for Virus Reactivation from Latency and Amplification during Immunosuppression. Journal of Clinical Medicine. 2019; 8 (9):1477.
Chicago/Turabian StyleDonald J. Alcendor. 2019. "BK Polyomavirus Virus Glomerular Tropism: Implications for Virus Reactivation from Latency and Amplification during Immunosuppression." Journal of Clinical Medicine 8, no. 9: 1477.
BK polyomavirus (BKV) reactivates from latency after immunosuppression in renal transplant patients, resulting in BKV-associated nephropathy (BKVAN). BKVAN has emerged as an important cause of graft dysfunction and graft loss among transplant patients. BKV infection in kidney transplant patients has increased over recent decades which correlates with the use of more potent immunosuppressive therapies. BKV infection of the Glomerular Vascular Unit (GVU) consisting of podocytes, mesangial cells, and glomerular endothelial cells could lead to glomerular inflammation and contribute to renal fibrosis. The effects of BKV on GVU infectivity have not been reported. We infected GVU cells with the Dunlop strain of BKV. Viral infectivity was analyzed by microscopy, immunofluorescence, Western blot analysis, and quantitative RT-PCR (qRT-PCR). The expression of specific proinflammatory cytokines induced by BKV was analyzed by qRT-PCR. BKV infection of podocytes, mesangial cells, and glomerular endothelial cells was confirmed by qRT-PCR and positive staining with antibodies to the BKV VP1 major capsid protein, or the SV40 Large T-Antigen. The increased transcriptional expression of interferon gamma-induced protein 10 (CXCL10/IP-10) and interferon beta (IFNβ) was detected in podocytes and mesangial cells at 96 h post-infection. All cellular components of the GVU are permissive for BKV replication. Cytopathic effects induced by BKV in podocytes and glomerular endothelial cells and the expression of CXCL10 and IFNβ genes by podocytes and mesangial cells may together contribute to glomerular inflammation and cytopathology in BKVAN.
Waldemar Popik; Atanu K. Khatua; Noyna F. Fabre; James E. K. Hildreth; Donald J. Alcendor. BK Virus Replication in the Glomerular Vascular Unit: Implications for BK Virus Associated Nephropathy. Viruses 2019, 11, 583 .
AMA StyleWaldemar Popik, Atanu K. Khatua, Noyna F. Fabre, James E. K. Hildreth, Donald J. Alcendor. BK Virus Replication in the Glomerular Vascular Unit: Implications for BK Virus Associated Nephropathy. Viruses. 2019; 11 (7):583.
Chicago/Turabian StyleWaldemar Popik; Atanu K. Khatua; Noyna F. Fabre; James E. K. Hildreth; Donald J. Alcendor. 2019. "BK Virus Replication in the Glomerular Vascular Unit: Implications for BK Virus Associated Nephropathy." Viruses 11, no. 7: 583.
Pericytes are multipotent cells of the vascular system with cytoplasmic extensions proximal to endothelial cells that occur along the abluminal surface of the endothelium. The interactions between endothelial cells and pericytes are essential for proper microvascular formation, development, stabilization, and maintenance. Pericytes are essential for the regulation of paracellular flow between cells, transendothelial fluid transport, angiogenesis, and vascular immunosurveillance. They also influence the chemical composition of the surrounding microenvironment to protect endothelial cells from potential harm. Dysregulation or loss of pericyte function can result in microvascular instability and pathological consequences. Human pericytes have been shown to be targets for human cytomegalovirus (HCMV) infection and lytic replication that likely contribute to vascular inflammation. This review focuses on human vascular pericytes and their permissiveness for HCMV infection. It also discusses their implication in pathogenesis in the blood⁻brain barrier (BBB), the inner blood⁻retinal barrier (IBRB), the placenta⁻blood barrier, and the renal glomerulus as well as their potential role in subclinical vascular disease.
Donald J. Alcendor. Human Vascular Pericytes and Cytomegalovirus Pathobiology. International Journal of Molecular Sciences 2019, 20, 1456 .
AMA StyleDonald J. Alcendor. Human Vascular Pericytes and Cytomegalovirus Pathobiology. International Journal of Molecular Sciences. 2019; 20 (6):1456.
Chicago/Turabian StyleDonald J. Alcendor. 2019. "Human Vascular Pericytes and Cytomegalovirus Pathobiology." International Journal of Molecular Sciences 20, no. 6: 1456.
High-level and persistent viruria observed in patients infected by Zika virus (ZIKV) has been well documented. However, renal pathology in acutely infected, immunocompetent patients remains subclinical. Moreover, the long-term impact of ZIKV infection, replication, and persistence in the renal compartment of adults and infants as well as immunosuppressed patients and solid organ transplant (SOT) recipients is unknown. Mechanisms involving host and viral factors that limit or control ZIKV pathogenesis in the renal compartment are important yet unexplored. The observation that long-term viral shedding occurs in the renal compartment in the absence of clinical disease requires further investigation. In this review, I explore Zika virus-induced renal pathology in animal models, the dynamics of virus shedding in urine, virus replication in glomerular cells, ZIKV infection in human renal transplantation, and the potential impact of long-term persistent ZIKV infection in the renal compartment.
Donald J. Alcendor. Zika virus infection and implications for kidney disease. Journal of Molecular Medicine 2018, 96, 1145 -1151.
AMA StyleDonald J. Alcendor. Zika virus infection and implications for kidney disease. Journal of Molecular Medicine. 2018; 96 (11):1145-1151.
Chicago/Turabian StyleDonald J. Alcendor. 2018. "Zika virus infection and implications for kidney disease." Journal of Molecular Medicine 96, no. 11: 1145-1151.
Zika virus (ZIKV) infection has been associated with microcephaly in infants. Currently there is no treatment or vaccine. Here we explore the use of a morpholino oligonucleotide targeted to the 5′ untranslated region (5′-UTR) of the ZIKV RNA to prevent ZIKV replication. Morpholino DWK-1 inhibition of ZIKV replication in human glomerular podocytes was examined by qRT-PCR, reduction in ZIKV genome copy number, western blot analysis, immunofluorescence and proinflammatory cytokine gene expression. Podocytes pretreated with DWK-1 showed reduced levels of both viral mRNA and ZIKV E protein expression compared to controls. We observed suppression in proinflammatory gene expression for IFN-β (interferon β) RANTES (regulated on activation, normal T cell expressed and secreted), MIP-1α (macrophage inflammatory protein-1α), TNF-α (tumor necrosis factor-α) and IL1-α (interleukin 1-α) in ZIKV-infected podocytes pretreated with DWK-1. Morpholino DWK-1 targeting the ZIKV 5′-UTR effectively inhibits ZIKV replication and suppresses ZIKV-induced proinflammatory gene expression.
Waldemar Popik; Atanu Khatua; James E.K. Hildreth; Benjamin Lee; Donald J. Alcendor. Phosphorodiamidate morpholino targeting the 5′ untranslated region of the ZIKV RNA inhibits virus replication. Virology 2018, 519, 77 -85.
AMA StyleWaldemar Popik, Atanu Khatua, James E.K. Hildreth, Benjamin Lee, Donald J. Alcendor. Phosphorodiamidate morpholino targeting the 5′ untranslated region of the ZIKV RNA inhibits virus replication. Virology. 2018; 519 ():77-85.
Chicago/Turabian StyleWaldemar Popik; Atanu Khatua; James E.K. Hildreth; Benjamin Lee; Donald J. Alcendor. 2018. "Phosphorodiamidate morpholino targeting the 5′ untranslated region of the ZIKV RNA inhibits virus replication." Virology 519, no. : 77-85.
Human Cytomegalovirus (HCMV) infection is problematic after kidney transplantation. Human mesangial cells along with human glomerular endothelial cells and podocytes constitute the renal glomerular vascular unit (GVU). HCMV infection of the GVU is poorly understood. GVU cells infectivity was analysed by microscopy and immunofluorescence. Cytokines profiles were measured by Luminex assays. Renal tissue analysis for HCMV infection was performed by immunohistochemistry. Mesangial cells and glomerular endothelial cells but not podocytes were permissive for both lab adapted and clinical strains of HCMV. Luminex analysis of cytokines expressed by mesangial cells exposed to the SBCMV clinical strain was examined. A Tricell infection model of the GVU maintains >90% viability with a unique cytokine profile. Finally, we show αSMA stained mesangial cells permissive for HCMV in renal tissue from a transplant patient. HCMV infection of mesangial cells induces angiogenic and proinflammatory cytokines that could contribute to glomerular inflammation.
Waldemar Popik; Hernan Correa; Atanu Khatua; David Aronoff; Donald J. Alcendor. Mesangial cells, specialized renal pericytes and cytomegalovirus infectivity: Implications for HCMV pathology in the glomerular vascular unit and post- transplant renal disease. Journal of Translational Science 2018, 5, 1 .
AMA StyleWaldemar Popik, Hernan Correa, Atanu Khatua, David Aronoff, Donald J. Alcendor. Mesangial cells, specialized renal pericytes and cytomegalovirus infectivity: Implications for HCMV pathology in the glomerular vascular unit and post- transplant renal disease. Journal of Translational Science. 2018; 5 (1):1.
Chicago/Turabian StyleWaldemar Popik; Hernan Correa; Atanu Khatua; David Aronoff; Donald J. Alcendor. 2018. "Mesangial cells, specialized renal pericytes and cytomegalovirus infectivity: Implications for HCMV pathology in the glomerular vascular unit and post- transplant renal disease." Journal of Translational Science 5, no. 1: 1.
David M. Aronoff; Hernan Correa; Lisa M. Rogers; Ravit Arav‐Boger; Donald J. Alcendor. Back Cover. American Journal of Reproductive Immunology 2017, 78, 1 .
AMA StyleDavid M. Aronoff, Hernan Correa, Lisa M. Rogers, Ravit Arav‐Boger, Donald J. Alcendor. Back Cover. American Journal of Reproductive Immunology. 2017; 78 (3):1.
Chicago/Turabian StyleDavid M. Aronoff; Hernan Correa; Lisa M. Rogers; Ravit Arav‐Boger; Donald J. Alcendor. 2017. "Back Cover." American Journal of Reproductive Immunology 78, no. 3: 1.
Problem Placental pericytes are essential for placental microvascular function, stability, and integrity. Mechanisms of human cytomegalovirus (HCMV) pathogenesis incorporating placental pericytes are unknown. Method of Study HCMV‐infected placental tissue was stained by dual‐labeled immunohistochemistry. Primary placental pericytes, cytotrophoblasts, and villous fibroblasts were exposed to HCMV; and infectivity was analyzed by microscopy and immunofluorescence. Cytokine expression was examined by Luminex assay. A HCMV‐GFP recombinant virus was used to examine replication kinetics. Results Immunohistochemistry showed HCMV in trophoblast and the villous core with T‐cell and macrophage infiltration. Primary HCMV isolate from a patient (SBCMV)‐ infected pericytes showed dysregulation of proinflammatory and angiogenic cytokines when compared to control cells. A tri‐cell model of the villous floor showed a unique expression profile. Finally, we show pericytes infected in vivo with HCMV in placental tissue from a congenitally infected child. Conclusion Placental pericytes support HCMV replication, inducing proinflammatory and angiogenic cytokines that likely contribute to viral dissemination, placenta inflammation, and dysregulation of placental angiogenesis.
David Aronoff; Hernan Correa; Lisa M. Rogers; Ravit Arav‐Boger; Donald J. Alcendor. Placental pericytes and cytomegalovirus infectivity: Implications forHCMVplacental pathology and congenital disease. American Journal of Reproductive Immunology 2017, 78, 1 .
AMA StyleDavid Aronoff, Hernan Correa, Lisa M. Rogers, Ravit Arav‐Boger, Donald J. Alcendor. Placental pericytes and cytomegalovirus infectivity: Implications forHCMVplacental pathology and congenital disease. American Journal of Reproductive Immunology. 2017; 78 (3):1.
Chicago/Turabian StyleDavid Aronoff; Hernan Correa; Lisa M. Rogers; Ravit Arav‐Boger; Donald J. Alcendor. 2017. "Placental pericytes and cytomegalovirus infectivity: Implications forHCMVplacental pathology and congenital disease." American Journal of Reproductive Immunology 78, no. 3: 1.
Zika virus (ZIKV) infection in the human renal compartment has not been reported. Several clinical reports have describe high-level persistent viral shedding in the urine of infected patients, but the associated mechanisms have not been explored until now. The current study examined cellular components of the glomerulus of the human kidney for ZIKV infectivity. I infected primary human podocytes, renal glomerular endothelial cells (GECs), and mesangial cells with ZIKV. Viral infectivity was analyzed by means of microscopy, immunofluorescence, real-time reverse-transcription polymerase chain reaction (RT-PCR), and quantitative RT-PCR (qRT-PCR), and the proinflammatory cytokines interleukin 1β, interferon β, and RANTES (regulated on activation of normal T cells expressed and secreted) were assessed using qRT-PCR. I show that glomerular podocytes, renal GECs, and mesangial cells are permissive for ZIKV infection. ZIKV infectivity was confirmed in all 3 cell types by means of immunofluorescence staining, RT-PCR, and qRT-PCR, and qRT-PCR analysis revealed increased transcriptional induction of interleukin 1β, interferon β, and RANTES in ZIKV-infected podocytes at 72 hours, compared with renal GECs and mesangial cells. The findings of this study support the notion that the glomerulus may serve as an amplification reservoir for ZIKV in the renal compartment. The impact of ZIKV infection in the human renal compartment is unknown and will require further study.
Donald J Alcendor. Zika Virus Infection of the Human Glomerular Cells: Implications for Viral Reservoirs and Renal Pathogenesis. Journal of Infectious Diseases 2017, 216, 162 -171.
AMA StyleDonald J Alcendor. Zika Virus Infection of the Human Glomerular Cells: Implications for Viral Reservoirs and Renal Pathogenesis. Journal of Infectious Diseases. 2017; 216 (2):162-171.
Chicago/Turabian StyleDonald J Alcendor. 2017. "Zika Virus Infection of the Human Glomerular Cells: Implications for Viral Reservoirs and Renal Pathogenesis." Journal of Infectious Diseases 216, no. 2: 162-171.
Ocular abnormalities present in microcephalic infants with presumed Zika virus (ZIKV) congenital disease includes focal pigment mottling of the retina, chorioretinal atrophy, optic nerve abnormalities, and lens dislocation. Target cells in the ocular compartment for ZIKV infectivity are unknown. The cellular response of ocular cells to ZIKV infection has not been described. Mechanisms for viral dissemination in the ocular compartment of ZIKV-infected infants and adults have not been reported. Here, we identify target cells for ZIKV infectivity in both the inner and outer blood-retinal barriers (IBRB and OBRB), describe the cytokine expression profile in the IBRB after ZIKV exposure, and propose a mechanism for viral dissemination in the retina. We expose primary cellular components of the IBRB including human retinal microvascular endothelial cells, retinal pericytes, and Müller cells as well as retinal pigmented epithelial cells of the OBRB to the PRVABC56 strain of ZIKV. Viral infectivity was analyzed by microscopy, immunofluorescence, and reverse transcription polymerase chain reaction (RT-PCR and qRT-PCR). Angiogenic and proinflammatory cytokines were measured by Luminex assays. We find by immunofluorescent staining using the Flavivirus 4G2 monoclonal antibody that retinal endothelial cells and pericytes of the IBRB and retinal pigmented epithelial cells of the OBRB are fully permissive for ZIKV infection but not Müller cells when compared to mock-infected controls. We confirmed ZIKV infectivity in retinal endothelial cells, retinal pericytes, and retinal pigmented epithelial cells by RT-PCR and qRT-PCR using ZIKV-specific oligonucleotide primers. Expression profiles by Luminex assays in retinal endothelial cells infected with ZIKV revealed a marginal increase in levels of beta-2 microglobulin (β2-m), granulocyte macrophage colony-stimulating factor (GMCSF), intercellular adhesion molecule 1 (ICAM-1), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP1), and vascular cell adhesion molecule 1 (VCAM-1) and higher levels of regulated upon activation, normal T cell expressed and presumably secreted (RANTES) but lower levels of interleukin-4 (IL-4) compared to controls. Retinal endothelial cells, retinal pericytes, and retinal pigmented epithelial cells are fully permissive for ZIKV lytic replication and are primary target cells in the retinal barriers for infection. ZIKV infection of retinal endothelial cells and retinal pericytes induces significantly higher levels of RANTES that likely contributes to ocular inflammation.
Tracoyia Roach; Donald J. Alcendor. Zika virus infection of cellular components of the blood-retinal barriers: implications for viral associated congenital ocular disease. Journal of Neuroinflammation 2017, 14, 1 -12.
AMA StyleTracoyia Roach, Donald J. Alcendor. Zika virus infection of cellular components of the blood-retinal barriers: implications for viral associated congenital ocular disease. Journal of Neuroinflammation. 2017; 14 (1):1-12.
Chicago/Turabian StyleTracoyia Roach; Donald J. Alcendor. 2017. "Zika virus infection of cellular components of the blood-retinal barriers: implications for viral associated congenital ocular disease." Journal of Neuroinflammation 14, no. 1: 1-12.
There is a health disparity for both bacterial vaginosis (BV) and human immunodeficiency virus type 1 (HIV-1) infection in African American women that may be linked. The evidence that BV predisposes women to higher risk for HIV infection is well documented. The underlying mechanisms to support the epidemiological connections will require further investigations. This review explores the risk factors for BV disease with implications for HIV-1 acquisition in the context of race as a potential driver of the 20-fold increase in HIV-1 acquisition for African American women compared to white women. Specifically, it explores (i) disparities for BV in African American women, (ii) racial disparity for HIV-1 acquisition in African American women, (iii) common factors associated with BV and HIV acquisition in African American women, and (iv) potential mechanisms of the enhancement of HIV-1 transmission by BV.
Donald J. Alcendor. Evaluation of Health Disparity in Bacterial Vaginosis and the Implications for HIV ‐1 Acquisition in African American Women. American Journal of Reproductive Immunology 2016, 76, 99 -107.
AMA StyleDonald J. Alcendor. Evaluation of Health Disparity in Bacterial Vaginosis and the Implications for HIV ‐1 Acquisition in African American Women. American Journal of Reproductive Immunology. 2016; 76 (2):99-107.
Chicago/Turabian StyleDonald J. Alcendor. 2016. "Evaluation of Health Disparity in Bacterial Vaginosis and the Implications for HIV ‐1 Acquisition in African American Women." American Journal of Reproductive Immunology 76, no. 2: 99-107.
Kaposi’s sarcoma (KS), a common cancer in individuals with HIV/AIDS, lacks a curative therapy. Few studies have examined changes in extracellular matrix (ECM) protein profiles in the development of KS. Here we used an in vitro (human dermal microvascular endothelial cells, DMVEC) and an in vivo mECK mouse model of Kaposi’s to study the impact of infection on tropoelastin. Using DMVEC, Kaposi’s sarcoma-associated herpesvirus (KSHV) reduced tropoelastin transcription when examined at 2, 5, 7, and 10 days post addition, a finding that was inversely correlated with a rise in viral latency associated nuclear antigen (LANA) transcription. Immunohistochemical/immunofluorescence data confirmed that DMVEC cells were KSHV-infected (evidenced by LANA production) and that there was a loss of tropoelastin protein compared to controls. Using the mECK36 mouse model of KS we observed a reduced expression of tropoelastin mRNA in 3 of 3 tumor biopsies compared to controls. Immunofluorescence staining showed high levels of viral LANA expression in the tumor core, while immunohistochemical staining showed high levels of LANA expression and spindle cells in tumors. Dual label immunohistochemistry on formalin-fixed paraffin-embedded tumor tissue revealed reduced expression of tropoelastin in LANA positive spindle cell regions quantified by Ariol SL-50 scanning analysis. Together, this suggests that alterations in tropoelastin may play an important role in the development of Kaposi’s and could serve as an early marker of this disease. This information will also allow us to explore the potential role of tropoelastin anti angiogenic properties in an in vivo model for KS disease.
Nald J. Alcendor. KSHV Down-regulates Tropoelastin in Both an in-vitro and in-vivo Kaposi’s Sarcoma Model. Journal of Oncobiomarkers 2015, 2, 1 -7.
AMA StyleNald J. Alcendor. KSHV Down-regulates Tropoelastin in Both an in-vitro and in-vivo Kaposi’s Sarcoma Model. Journal of Oncobiomarkers. 2015; 2 (1):1-7.
Chicago/Turabian StyleNald J. Alcendor. 2015. "KSHV Down-regulates Tropoelastin in Both an in-vitro and in-vivo Kaposi’s Sarcoma Model." Journal of Oncobiomarkers 2, no. 1: 1-7.