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https://www.readbyqxmd.com/read/27914937/mcl-1-small-molecule-inhibitors-encapsulated-into-nanoparticles-exhibit-increased-killing-efficacy-towards-hcmv-infected-monocytes
#1
Christine M Burrer, Helen Auburn, Xu Wang, Juntao Luo, Fardokht A Abulwerdi, Zaneta Nikolovska-Coleska, Gary C Chan
Human cytomegalovirus (HCMV) spreads and establishes a persistent infection within a host by stimulating the survival of carrier myeloid cells via the upregulation of Mcl-1, an antiapoptotic member of the Bcl-2 family of proteins. However, the lack of potent Mcl-1-specific inhibitors and a targetable delivery system has limited to ability to exploit Mcl-1 as a therapeutic strategy to eliminate HCMV-infected monocytes. In this study, we found a lead compound from a novel class of Mcl-1 small-molecule inhibitors rapidly induced death of HCMV-infected monocytes...
November 30, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27907183/activation-of-innate-and-adaptive-immunity-by-a-recombinant-human-cytomegalovirus-strain-expressing-an-nkg2d-ligand
#2
Adriana Tomić, Pavankumar R Varanasi, Mijo Golemac, Suzana Malić, Peggy Riese, Eva M Borst, Eva Mischak-Weissinger, Carlos A Guzmán, Astrid Krmpotić, Stipan Jonjić, Martin Messerle
Development of an effective vaccine against human cytomegalovirus (HCMV) is a need of utmost medical importance. Generally, it is believed that a live attenuated vaccine would best provide protective immunity against this tenacious pathogen. Here, we propose a strategy for an HCMV vaccine that aims at the simultaneous activation of innate and adaptive immune responses. An HCMV strain expressing the host ligand ULBP2 for the NKG2D receptor was found to be susceptible to control by natural killer (NK) cells, and preserved the ability to stimulate HCMV-specific T cells...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27903803/the-human-cytomegalovirus-ie1-protein-antagonizes-pml-nuclear-body-mediated-intrinsic-immunity-via-the-inhibition-of-pml-de-novo-sumoylation
#3
Eva-Maria Schilling, Myriam Scherer, Nina Reuter, Johannes Schweininger, Yves A Muller, Thomas Stamminger
: PML nuclear bodies (NBs) are accumulations of cellular proteins embedded in a scaffold-like structure built by SUMO-modified PML/TRIM19. PML and other NB proteins act as cellular restriction factors against human cytomegalovirus (HCMV), however, this intrinsic defense is counteracted by the immediate-early protein 1 (IE1) of HCMV. IE1 directly interacts with the PML coiled-coil domain via its globular core region and disrupts NB foci by inducing a loss of PML SUMOylation. Here, we demonstrate that IE1 acts via abrogating the de novo SUMOylation of PML...
November 30, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27902356/luciferase-tagged-wild-type-and-tropism-deficient-mouse-cytomegaloviruses-reveal-early-dynamics-of-host-colonization-following-peripheral-challenge
#4
Helen Farrell, Martha Oliveira, Kate Macdonald, Joseph Yunis, Michael Mach, Kimberley Bruce, Philip Stevenson, Rhonda Cardin, Nicholas Davis-Poynter
Cytomegaloviruses (CMVs) establish persistent, systemic infections and cause disease by maternal-fetal transfer, suggesting that their dissemination is a key target for anti-viral intervention. Late clinical presentation has meant that human CMV dissemination is not well understood. Murine CMV provides a tractable model. Whole mouse imaging of virus-expressed luciferase has proved a useful way to track systemic infections. MCMV, in which the abundant lytic gene M78 was luciferase tagged via a self-cleaving peptide (M78-LUC), allowed serial, unbiased imaging of systemic and peripheral infection without significant virus attenuation...
October 26, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27894857/cytokine-induced-memory-like-differentiation-enhances-unlicensed-nk-cell-anti-leukemia-and-fc%C3%AE-riiia-triggered-responses
#5
Julia A Wagner, Melissa M Berrien-Elliott, Maximillian Rosario, Jeffrey W Leong, Brea A Jewell, Timothy Schappe, Sara Abdel-Latif, Todd A Fehniger
Cytokine-induced memory-like natural killer (NK) cells differentiate following short-term pre-activation with interleukin (IL)-12, IL-15, and IL-18 and display enhanced effector function in response to cytokines or tumor targets for weeks following the initial pre-activation. Conventional NK cell function is dependent upon a licensing signal, classically delivered by an inhibitory receptor engaging its cognate MHC class I ligand. How licensing status integrates with cytokine-induced memory-like NK cell responses is unknown...
November 25, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27888673/clinical-correlates-of-pp65-antigenemia-monitoring-in-the-first-months-of-post-kidney-transplant-in-patients-undergoing-universal-prophylaxis-or-preemptive-therapy
#6
Fabiana Rabe Carvalho, Rachel Ingrid Juliboni Cosendey, Cintia Fernandes Souza, Thalia Medeiros, Paulo Alexandre Menezes, Andrea Alice Silva, Jorge Reis Almeida, Jocemir Ronaldo Lugon
INTRODUCTION: Human cytomegalovirus (HCMV) is a major cause of morbidity in kidney transplant patients. OBJECTIVES: We aimed to study viral replication and serological response in the first months post kidney transplant in patients undergoing universal prophylaxis or preemptive therapy and correlate the findings with the clinical course of HCMV infection. PATIENTS AND METHODS: Independent from the clinical strategy adopted for managing HCMV infection, prophylaxis versus preemptive therapy, the pp65 antigenemia assay and serological response were assessed on the day of transplantation, and then weekly during the first three months of post-transplant...
November 23, 2016: Brazilian Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27887982/genotypic-resistance-of-cytomegalovirus-to-antivirals-in-hematopoietic-stem-cell-transplant-recipients-from-portugal-a-retrospective-study
#7
Ana Bela Campos, Joana Ribeiro, Carlos Pinho Vaz, Fernando Campilho, Rosa Branca, António Campos, Inês Baldaque, Rui Medeiros, David Boutolleau, Hugo Sousa
The aim of this study was to characterize Human Cytomegalovirus (HCMV) drug resistance mutations in UL97 and UL54 genes in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients in Portugal. We have performed a retrospective study with 22 patients from a cohort of patients with different haematological malignancies submitted to allo-HSCT between 2010 and 2014. Patients were selected according to clinical and laboratory data of HCMV infection and management. HCMV resistance mutations were characterized by sequencing of UL97 and UL54 genes...
November 22, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27882457/cytomegalovirus-vaccines-current-status-and-future-prospects
#8
REVIEW
K M Anderholm, C J Bierle, M R Schleiss
Congenital human cytomegalovirus (HCMV) infection can result in severe and permanent neurological injury in newborns, and vaccine development is accordingly a major public health priority. HCMV can also cause disease in solid organ transplant (SOT) and hematopoietic stem-cell transplant (HSCT) recipients, and a vaccine would be valuable in prevention of viremia and end-organ disease in these populations. Currently there is no licensed HCMV vaccine, but progress toward this goal has been made in recent clinical trials...
November 2016: Drugs
https://www.readbyqxmd.com/read/27861998/a-two-step-screening-approach-for-the-identification-of-blood-donors-with-highly-and-broadly-neutralizing-capacities-against-human-cytomegalovirus
#9
Jessica J Falk, Martina Winkelmann, Hubert Schrezenmeier, Dagmar Stöhr, Christian Sinzger, Ramin Lotfi
BACKGROUND: Hyperimmunoglobulins are frequently applied for prophylaxis and treatment of human cytomegalovirus (HCMV) infections but were only marginally effective in meta-analyses of clinical studies. This might be partially due to selection of donors rather for total anti-HCMV titers than for neutralizing capacities. To improve efficacy against HCMV infection, we aimed at developing a high-throughput screening method for identification of blood donors with highly and broadly neutralizing capacities...
November 10, 2016: Transfusion
https://www.readbyqxmd.com/read/27856764/role-of-nucleotide-binding-oligomerization-domain-1-nod1-and-its-variants-in-human-cytomegalovirus-control-in-vitro-and-in-vivo
#10
Yi-Hsin Fan, Sujayita Roy, Rupkatha Mukhopadhyay, Arun Kapoor, Priya Duggal, Genevieve L Wojcik, Robert F Pass, Ravit Arav-Boger
Induction of nucleotide-binding oligomerization domain 2 (NOD2) and downstream receptor-interacting serine/threonine-protein kinase 2 (RIPK2) by human cytomegalovirus (HCMV) is known to up-regulate antiviral responses and suppress virus replication. We investigated the role of nucleotide-binding oligomerization domain 1 (NOD1), which also signals through RIPK2, in HCMV control. NOD1 activation by Tri-DAP (NOD1 agonist) suppressed HCMV and induced IFN-β. Mouse CMV was also inhibited through NOD1 activation...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27844024/peroxisome-proliferator-activated-receptor-%C3%AE-ppar%C3%AE-activation-a-key-determinant-of-neuropathogeny-during-congenital-infection-by-cytomegalovirus
#11
COMMENT
Stéphane Chavanas
Congenital infection by human cytomegalovirus (HCMV) might result in permanent neurological sequelae, including sensorineural deafness, cerebral palsies or devastating neurodevelopmental abnormalities. We recently disclosed that Peroxisome Proliferator-Activated Receptor gamma (PPARγ), a transcription factor of the nuclear receptor superfamily, is a key determinant of HCMV pathogenesis in developing brain. Using neural stem cells from human embryonic stem cells, we showed that HCMV infection strongly increases levels and activity of PPARγ in NSCs...
2016: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/27829026/cross-species-rhesus-cytomegalovirus-infection-of-cynomolgus-macaques
#12
Benjamin J Burwitz, Daniel Malouli, Benjamin N Bimber, Jason S Reed, Abigail B Ventura, Meaghan H Hancock, Luke S Uebelhoer, Amruta Bhusari, Katherine B Hammond, Renee G Espinosa Trethewy, Alex Klug, Alfred W Legasse, Michael K Axthelm, Jay A Nelson, Byung S Park, Daniel N Streblow, Scott G Hansen, Louis J Picker, Klaus Früh, Jonah B Sacha
Cytomegaloviruses (CMV) are highly species-specific due to millennia of co-evolution and adaptation to their host, with no successful experimental cross-species infection in primates reported to date. Accordingly, full genome phylogenetic analysis of multiple new CMV field isolates derived from two closely related nonhuman primate species, Indian-origin rhesus macaques (RM) and Mauritian-origin cynomolgus macaques (MCM), revealed distinct and tight lineage clustering according to the species of origin, with MCM CMV isolates mirroring the limited genetic diversity of their primate host that underwent a population bottleneck 400 years ago...
November 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27826043/the-interaction-between-human-papillomavirus-and-other-viruses
#13
REVIEW
J T Guidry, R S Scott
The etiological role of human papillomavirus (HPV) in anogenital tract and head and neck cancers is well established. However, only a low percentage of HPV-positive women develop cancer, indicating that HPV is necessary but not sufficient in carcinogenesis. Several biological and environmental cofactors have been implicated in the development of HPV-associated carcinoma that include immune status, hormonal changes, parity, dietary habits, tobacco usage, and co-infection with other sexually transmissible agents...
November 5, 2016: Virus Research
https://www.readbyqxmd.com/read/27825854/establishment-and-validation-of-an-enzyme-linked-immunosorbent-assay-for-igg-antibody-against-cytomegalovirus-based-on-pp150-antigen
#14
Huang Xi, Li Jinjie, Ge Shengxiang, Li Tingdong, Wang Han, Guo Xiaoyi, Fu Tong-Ming, Zhang Jun
The development of HCMV vaccines for the prevention of congenital HCMV has been identified as a top priority by the Institute of Medicine (USA), and virus infection is an important endpoint for the efficacy evaluation of the candidate vaccines. However, it is technically difficult to capture the HCMV viremia or uremia in infected individuals because the viremia or uremia can be detected only transiently during acute infection, and most people who are infected are asymptomatic. Thus, it is much desired to develop a serological assay for effectively distinguishing anti-HCMV antibodies as a result of natural infection from those elicited by subunit antigen vaccination...
November 4, 2016: Journal of Virological Methods
https://www.readbyqxmd.com/read/27824944/human-cytomegalovirus-mir-ul148d-facilitates-latent-viral-infection-by-targeting-host-cell-immediate-early-response-gene-5
#15
Chaoyun Pan, Dihan Zhu, Yan Wang, Limin Li, Donghai Li, Fenyong Liu, Chen-Yu Zhang, Ke Zen
The mechanisms underlying human cytomegalovirus (HCMV) latency remain incompletely understood. Here, we showed that a HCMV-encoded miRNA, miR-UL148D, robustly accumulates during late stages of experimental latent HCMV infection in host cells and promotes HCMV latency by modulating the immediate early response gene 5 (IER5)-cell division cycle 25B (CDC25B) axis in host cells. miR-UL148D inhibited IER5 expression by directly targeting the three-prime untranslated region(3'UTR) of IER5 mRNA and thus rescued CDC25B expression during the establishment of viral latency...
November 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27815125/meeting-report-29th-international-conference-on-antiviral-research-in-la-jolla-ca-usa
#16
REVIEW
R Anthony Vere Hodge
The 29th International Conference on Antiviral Research (ICAR) was held in La Jolla, CA, USA from April 17 to 21, 2016. This report opens with a tribute to the late Chris McGuigan, a Past-President of ISAR, then continues with summaries of the principal invited lectures. Doug Richman (Elion Award) investigated HIV resistance, Bob Vince (Holý Award) showed how carbocyclic nucleoside analogs led to abacavir and Jerome Deval (Prusoff Award) explained how his group chose to seek a nucleoside analog to treat RSV...
November 1, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27797961/a-replication-defective-human-cytomegalovirus-vaccine-for-prevention-of-congenital-infection
#17
Dai Wang, Daniel C Freed, Xi He, Fengsheng Li, Aimin Tang, Kara S Cox, Sheri A Dubey, Suzanne Cole, Muneeswara Babu Medi, Yaping Liu, Jingyuan Xu, Zhi-Qiang Zhang, Adam C Finnefrock, Liping Song, Amy S Espeseth, John W Shiver, Danilo R Casimiro, Tong-Ming Fu
Congenital human cytomegalovirus (HCMV) infection occurs in ~0.64% of infants born each year in the United States and is the leading nongenetic cause of childhood neurodevelopmental disabilities. No licensed HCMV vaccine is currently available. Natural immunity to HCMV in women before pregnancy is associated with a reduced risk of fetal infection, suggesting that a vaccine is feasible if it can reproduce immune responses elicited by natural infection. On the basis of this premise, we developed a whole-virus vaccine candidate from the live attenuated AD169 strain, with genetic modifications to improve its immunogenicity and attenuation...
October 26, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27795424/potent-inhibition-of-hcmv-by-modulating-the-cellular-snare-syntaxin-5
#18
Linda Cruz, Nicholas T Streck, Kevin Ferguson, Trisha Desai, Dhimant H Desai, Shantu G Amin, Nicholas J Buchkovich
: Formation of the cytoplasmic viral assembly compartment (cVAC) is an important step for efficient HCMV assembly. To do this, the virus must alter and repurpose the normal cellular balance of membrane and protein flux, a process that is not well understood. Although a recent screen identified three viral proteins essential for cVAC formation, less is known about the contribution of cellular factors. We show that HCMV infection increases the protein level of a cellular trafficking factor, Syntaxin 5 (STX5), a member of the syntaxin family of SNARE proteins...
October 19, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27795411/importance-of-highly-conserved-peptide-sites-of-hcmv-go-for-the-formation-of-the-gh-gl-go-complex
#19
Cora Stegmann, Mohamed E A Abdellatif, Kerstin Laib Sampaio, Paul Walther, Christian Sinzger
: The glycoprotein O (gO) is betaherpesvirus-specific. Together with the viral glycoproteins H and L, gO forms a covalent trimeric complex that is part of the viral envelope. This trimer is crucial for cell-free infectivity of human cytomegalovirus (HCMV) but dispensable for cell-associated spread. We hypothesized that the amino acids (aa) that are conserved among gOs of different cytomegaloviruses are important for the formation of the trimeric complex and hence for efficient virus spread...
October 19, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27795301/additive-protection-against-congenital-cmv-conferred-by-combined-gb-pp65-vaccination-using-a-lymphocytic-choriomeningitis-virus-lcmv-vector
#20
Mark R Schleiss, Ursula Berka, Elizabeth Watson, Mario Aistleithner, Bettina Kiefmann, Bastien Mangeat, Elizabeth C Swanson, Peter A Gillis, Nelmary Hernandez-Alvarado, Claudia Fernández-Alarcón, Jason C Zabeli, Daniel D Pinschewer, Anders Lilja, Michael Schwendinger, Farshad Guirakhoo, Thomas P Monath, Klaus Orlinger
Subunit vaccines for prevention of congenital cytomegalovirus (CMV) infection based on glycoprotein B (gB) and pp65 are in clinical trials, but it is unclear whether simultaneous vaccination with both antigens enhances protection. We undertook evaluation of a novel bivalent vaccine based on non-replicating lymphocytic choriomeningitis virus (rLCMV) vectors expressing a cytoplasmic tail-deleted gB (gB(dCt)), and full-length pp65 from human CMV in mice. Immunization with the gB(dCt) vector alone elicited a comparable gB-binding antibody response, and a superior neutralizing response, to that elicited by adjuvanted subunit gB...
October 26, 2016: Clinical and Vaccine Immunology: CVI
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