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https://www.readbyqxmd.com/read/28077659/hiv-controllers-exhibit-enhanced-frequencies-of-mhc-class-ii-tetramer-gag-specific-cd4-t-cells-in-chronic-clade-c-hiv-1-infection
#1
Faatima Laher, Srinika Ranasinghe, Filippos Porichis, Nikoshia Mewalal, Karyn Pretorius, Nasreen Ismail, Søren Buus, Anette Stryhn, Mary Carrington, Bruce D Walker, Thumbi Ndung'u, Zaza M Ndhlovu
: Immune control of viral infections is heavily dependent on helper CD4(+) T cell function. However, understanding the contribution of HIV-specific CD4(+) T cell responses to immune protection against HIV-1, particularly in clade C infection remains incomplete. Recently, MHC class II tetramers have emerged as a powerful tool for interrogating antigen specific CD4(+) T cells without relying on effector functions. Here, we defined the MHC class II alleles for immunodominant Gag CD4(+) T cell epitopes in clade C virus infection, constructed MHC class II tetramers, and then used these to define the magnitude, function, and relation to viral load of HIV-specific CD4(+) T cell responses in a cohort of untreated HIV clade C infected persons...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077649/tcr-clonotype-specific-differences-in-inhibitory-activity-of-hiv-1-cytotoxic-t-cell-clones-is-not-mediated-by-tcr-alone
#2
Nina C Flerin, Huabiao Chen, Tynisha D Glover, Pedro A Lamothe, Jian Hua Zheng, Justin W Fang, Zaza M Ndhlovu, Evan W Newell, Mark M Davis, Bruce D Walker, Harris Goldstein
: Functional analysis of T cell responses in HIV-infected individuals has indicated that virus-specific CD8(+) T cells with superior antiviral efficacy are well represented in HIV-1 controllers but are rare or absent in HIV-1 progessors. To define the role of individual TCR clonotypes in differential antiviral CD8(+) T cell function, we performed detailed functional and mass cytometric cluster analysis of multiple CD8(+) T cell clones recognizing the identical HLA-B*2705-restricted HIV-1 epitope KK10 (KRWIILGLNK)...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077601/a-new-rna-based-adjuvant-enhances-virus-specific-vaccine-responses-by-locally-triggering-tlr-and-rlh-dependent-effects
#3
Annett Ziegler, Claudia Soldner, Stefan Lienenklaus, Julia Spanier, Stephanie Trittel, Peggy Riese, Thomas Kramps, Siegfried Weiss, Regina Heidenreich, Edith Jasny, Carlos A Guzmán, Karl-Josef Kallen, Mariola Fotin-Mleczek, Ulrich Kalinke
Among innovative adjuvants conferring a Th1-shift, RNAdjuvant is a promising candidate. This adjuvant consists of a 547-nt uncapped noncoding ssRNA containing polyU repeats that is stabilized by a cationic carrier peptide. Whereas vaccination of mice with an influenza subunit vaccine induced moderate virus-specific IgG1, vaccination together with RNAdjuvant significantly enhanced this IgG1 and additionally promoted the formation of IgG2b/c, which is indicative of Th1 responses. Furthermore, such sera neutralized influenza virus, whereas this effect was not detected upon vaccination with the subunit vaccine alone...
January 11, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28077074/single-and-multiple-viral-respiratory-infections-in-children-disease-and-management-cannot-be-related-to-a-specific-pathogen
#4
Jérôme O Wishaupt, Tjeerd van der Ploeg, Ronald de Groot, Florens G A Versteegh, Nico G Hartwig
BACKGROUND: The number of viral pathogens associated with pediatric acute respiratory tract infection (ARI) has grown since the introduction of reverse transcription real-time polymerase chain reaction (RT-PCR) assays. Multiple viruses are detected during a single ARI episode in approximately a quarter of all cases. The clinical relevance of these multiple detections is unclear, as is the role of the individual virus. We therefore investigated the correlation between clinical data and RT-PCR results in children with single- and multiple viral ARI...
January 11, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28072682/increasing-lag-3-expression-suppresses-t-cell-function-in-chronic-hepatitis-b-a-balance-between-immunity-strength-and-liver-injury-extent
#5
Bo Ye, Xuefen Li, Yuejiao Dong, Yiyin Wang, Li Tian, Sha Lin, Xia Liu, Haishen Kong, Yu Chen
Weak or absent virus-specific CD8 T-cell responses to hepatitis B virus (HBV) infection are thought to be responsible for persistent HBV infection. Previous studies have indicated that multiple inhibitory receptors, including lymphocyte activation gene-3 (LAG-3), can suppress the CD8 T-cell response in chronic viral infection. This study aimed to detect LAG-3 expression and to investigate the manner in which the immune response is regulated to balance the strength of the response with the extent of liver injury in chronic HBV infection...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28067290/chimeric-virus-like-particles-containing-influenza-ha-antigen-and-gpi-ccl28-induce-long-lasting-mucosal-immunity-against-h3n2-viruses
#6
Teena Mohan, Zachary Berman, Yuan Luo, Chao Wang, Shelly Wang, Richard W Compans, Bao-Zhong Wang
Influenza virus is a significant cause of morbidity and mortality, with worldwide seasonal epidemics. The duration and quality of humoral immunity and generation of immunological memory to vaccines is critical for protective immunity. In the current study, we examined the long-lasting protective efficacy of chimeric VLPs (cVLPs) containing influenza HA and GPI-anchored CCL28 as antigen and mucosal adjuvant, respectively, when immunized intranasally in mice. We report that the cVLPs induced significantly higher and sustainable levels of virus-specific antibody responses, especially IgA levels and hemagglutination inhibition (HAI) titers, more than 8-month post-vaccination compared to influenza VLPs without CCL28 or influenza VLPs physically mixed with sCCL28 (soluble) in mice...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28063344/reducing-persistent-polyomavirus-infection-increases-functionality-of-virus-specific-memory-cd8-t-cells
#7
Qingsong Qin, Matthew Lauver, Saumya Maru, Eugene Lin, Aron E Lukacher
Mouse polyomavirus (MuPyV) causes a smoldering persistent infection in immunocompetent mice. To lower MuPyV infection in acutely and persistently infected mice, and study the impact of a temporal reduction in viral loads on the memory CD8 T cell response, we created a recombinant MuPyV in which a loxP sequence was inserted into the A2 strain genome upstream of the early promoter and another loxP sequence was inserted in cis into the intron shared by all three T antigens. Using mice transgenic for tamoxifen-inducible Cre recombinase, we demonstrated that reduction in MuPyV load during persistent infection was associated with differentiation of virus-specific CD8 T cells having a superior recall response...
January 4, 2017: Virology
https://www.readbyqxmd.com/read/28060314/analysis-of-simian-immunodeficiency-virus-specific-cd8-t-cells-in-rhesus-macaques-by-peptide-mhc-i-tetramer-staining
#8
Lucas Gonzalez-Nieto, Aline Domingues, Michael Ricciardi, Martin J Gutman, Helen S Maxwell, Nuria Pedreño-Lopez, Varian Bailey, Diogo M Magnani, Mauricio A Martins
Peptide-major histocompatibility complex class I (pMHC-I) tetramers have been an invaluable tool to study CD8(+) T-cell responses. Because these reagents directly bind to T-cell receptors on the surface of CD8(+) T-lymphocytes, fluorochrome-labeled pMHC-I tetramers enable the accurate detection of antigen (Ag)-specific CD8(+) T-cells without the need for in vitro re-stimulation. Moreover, when combined with multi-color flow cytometry, pMHC-I tetramer staining can reveal key aspects of Ag-specific CD8(+) T-cells, including differentiation stage, memory phenotype, and activation status...
December 23, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28060008/acute-hiv-1-infection-is-associated-with-increased-plasma-levels-of-heme-oxygenase-1-ho-1-and-presence-of-ho-1-specific-regulatory-t-cells
#9
Mathieu Angin, Anahita Fathi, Melanie King, Mary B Ledoux, Alicja Piechocka-Trocha, Marcus Altfeld, Marylyn M Addo
OBJECTIVE: Heme-oxygenase-1 (HO-1) is an inducible stress-response protein with potent anti-inflammatory activity and recent data suggest a potentially beneficial role in HIV pathogenesis. We here investigated the impact of HO-1 and a novel subset of HO-1-specific CD8 regulatory T cells on virus-specific T cell immunity in HIV-1-infected individuals. METHODS: HO-1 protein levels were quantified in plasma from individuals at different stages of HIV-1 disease and longitudinally following primary HIV infection...
January 4, 2017: AIDS
https://www.readbyqxmd.com/read/28041959/substrate-selectivity-of-dengue-and-zika-virus-ns5-polymerase-towards-2-modified-nucleotide-analogues
#10
Supanee Potisopon, François Ferron, Véronique Fattorini, Barbara Selisko, Bruno Canard
In targeting the essential viral RNA-dependent RNA-polymerase (RdRp), nucleotide analogues play a major role in antiviral therapies. In the Flaviviridae family, the hepatitis C virus (HCV) can be eradicated from chronically infected patients using a combination of drugs which generally include the 2'-modified uridine analogue Sofosbuvir, delivered as nucleotide prodrug. Dengue and Zika viruses are emerging flaviviruses whose RdRp is closely related to that of HCV, yet no nucleoside drug has been clinically approved for these acute infections...
December 29, 2016: Antiviral Research
https://www.readbyqxmd.com/read/28035603/reovirus-safety-study-for-proliferation-and-differentiation-of-human-adipose-derived-mesenchymal-stem-cells
#11
Jeong-Soo Park, Manbok Kim
Naturally occurring reoviruses are live replication-proficient viruses specifically infecting human cancer cells while sparing the normal counterparts. Stem cells can be highly susceptible to viral infection due to their innate high proliferation potential and other active signaling pathways of cells that might be involved in viral tropism. In the previous study, we showed that reoviruses could adversely affect murine embryonic stem cells' integrity in vitro and in vivo. Oncolytic viruses, delivered systemically face many hurdles that also impede their localization and infection of, metastatic tumors, due to a variety of immune and physical barriers...
January 2017: Journal of Microbiology / the Microbiological Society of Korea
https://www.readbyqxmd.com/read/28031335/nkg2c-e-marks-the-unique-cytotoxic-cd4-t-cell-subset-thctl-generated-by-influenza-infection
#12
Nikki B Marshall, Allen M Vong, Priyadharshini Devarajan, Matthew D Brauner, Yi Kuang, Ribhu Nayar, Elizabeth A Schutten, Catherine H Castonguay, Leslie J Berg, Stephen L Nutt, Susan L Swain
CD4 T cells can differentiate into multiple effector subsets, including ThCTL that mediate MHC class II-restricted cytotoxicity. Although CD4 T cell-mediated cytotoxicity has been reported in multiple viral infections, their characteristics and the factors regulating their generation are unclear, in part due to a lack of a signature marker. We show in this article that, in mice, NKG2C/E identifies the ThCTL that develop in the lung during influenza A virus infection. ThCTL express the NKG2X/CD94 complex, in particular the NKG2C/E isoforms...
December 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28018990/the-tcf1-bcl6-axis-counteracts-type-i-interferon-to-repress-exhaustion-and-maintain-t-cell-stemness
#13
Tuoqi Wu, Yun Ji, E Ashley Moseman, Haifeng C Xu, Monica Manglani, Martha Kirby, Stacie M Anderson, Robin Handon, Elizabeth Kenyon, Abdel Elkahloun, Weiwei Wu, Philipp A Lang, Luca Gattinoni, Dorian B McGavern, Pamela L Schwartzberg
During chronic viral infections and in cancer, T cells become dysfunctional, a state known as T cell exhaustion. Although it is well recognized that memory CD8 T cells account for the persistence of CD8 T cell immunity after acute infection, how exhausted T cells persist remains less clear. Using chronic infection with lymphocytic choriomeningitis virus clone 13 and tumor samples, we demonstrate that CD8 T cells differentiate into a less exhausted TCF1(high) and a more exhausted TCF1(low) population. Virus-specific TCF1(high) CD8 T cells, which resemble T follicular helper (TFH) cells, persist and recall better than do TCF1(low) cells and act as progenitor cells to replenish TCF1(low) cells...
December 23, 2016: Science Immunology
https://www.readbyqxmd.com/read/28012212/incidence-of-serum-antibody-titers-against-varicella-zoster-virus-in-japanese-patients-with-herpes-zoster
#14
Motoko Miyachi, Honoka Ihara, Shinichi Imafuku
Herpes zoster is an internal reactivation of varicella zoster virus following establishment of latent infection in the dorsal root ganglia during primary infection, which presents as chickenpox. Therefore, serologically, herpes zoster patients already have anti-varicella zoster virus immunoglobulin G at the onset of disease. Hence, positive serum antibody does not confirm the diagnosis of herpes zoster. We retrospectively investigated the incidence of varicella zoster virus-specific complement fixation in 865 zoster patients at initial presentation to a dermatology clinic...
December 24, 2016: Journal of Dermatology
https://www.readbyqxmd.com/read/28008927/immunotherapy-against-cancer-related-viruses
#15
REVIEW
Haruko Tashiro, Malcolm K Brenner
Approximately 12% of all cancers worldwide are associated with viral infections. To date, eight viruses have been shown to contribute to the development of human cancers, including Epstein-Barr virus (EBV), Hepatitis B and C viruses, and Human papilloma virus, among others. These DNA and RNA viruses produce oncogenic effects through distinct mechanisms. First, viruses may induce sustained disorders of host cell growth and survival through the genes they express, or may induce DNA damage response in host cells, which in turn increases host genome instability...
January 2017: Cell Research
https://www.readbyqxmd.com/read/28006034/peripheral-organs-of-dengue-fatal-cases-present-strong-pro-inflammatory-response-with-participation-of-ifn-gamma-tnf-alpha-and-rantes-producing-cells
#16
Tiago F Póvoa, Edson R A Oliveira, Carlos A Basílio-de-Oliveira, Gerard J Nuovo, Vera L A Chagas, Natália G Salomão, Ester M Mota, Marciano V Paes
Dengue disease is an acute viral illness caused by dengue virus (DENV) that can progress to hemorrhagic stages leading to about 20000 deaths every year worldwide. Despite many clinical investigations regarding dengue, the immunopathogenic process by which infected patients evolve to the severe forms is not fully understood. Apart from differences in virulence and the antibody cross reactivity that can potentially augment virus replication, imbalanced cellular immunity is also seen as a major concern in the establishment of severe dengue...
2016: PloS One
https://www.readbyqxmd.com/read/28004418/sublingual-immunization-with-japanese-encephalitis-virus-vaccines-induces-effective-immunity-through-both-cellular-and-humoral-immune-responses-in-mice
#17
Eun-Young Lee, Joo-Young Kim, Deuk-Ki Lee, Il-Sub Yoon, Hae Li Ko, Ji-Woo Chung, Jun Chang, Jae-Hwan Nam
The Japanese encephalitis virus (JEV) is the leading cause of viral encephalitis. Although there are four classes of vaccines against JEV, the immunization routes for all vaccines are subcutaneous or intramuscular injection. In here, we investigated the effectiveness of sublingual administration of the JEV live-attenuated vaccine or the recombinant modified vaccinia virus Ankara (MVA) vaccine including JEV prM/E. The mice were immunized three times intramuscularly (i.m.) or sublingually (s.l.). One week after the final immunization by both s...
December 22, 2016: Microbiology and Immunology
https://www.readbyqxmd.com/read/28003150/concomitant-helminth-infection-downmodulates-the-vaccinia-virus-specific-immune-response-and-potentiates-virus-associated-pathology
#18
Pedro Henrique Gazzinelli-Guimarães, Lorena Falabella Daher de Freitas, Ana Clara Gazzinelli-Guimarães, Fabiana Coelho, Fernando Sérgio Barbosa, Denise Nogueira, Chiara Amorim, Lucas de Carvalho Dhom-Lemos, Luciana Maria Oliveira, Alexandre Barcelos da Silveira, Flávio Guimarães da Fonseca, Lilian Lacerda Bueno, Ricardo Toshio Fujiwara
The aim of this work was to elucidate the immunopathological mechanisms of how helminths may influence the course of a viral infection, using a murine model. Severe virulence, a relevant increase in the virus titres in the lung and a higher mortality rate were observed in Ascaris and Vaccinia virus (VACV) co-infected mice, compared with VACV mono-infected mice. Immunopathological analysis suggested that the ablation of CD8(+) T cells, the marked reduction of circulating CD4(+) T cells producing IFN-γ, and the robust pulmonary inflammation were associated with the increase of morbidity/mortality in co-infection and subsequently with the negative impact of concomitant pulmonary ascariasis and respiratory VACV infection for the host...
December 18, 2016: International Journal for Parasitology
https://www.readbyqxmd.com/read/28002473/role-of-occult-and-post-acute-phase-replication-in-protective-immunity-induced-with-a-novel-live-attenuated-siv-vaccine
#19
Neil Berry, Maria Manoussaka, Claire Ham, Deborah Ferguson, Hannah Tudor, Giada Mattiuzzo, Bep Klaver, Mark Page, Richard Stebbings, Atze T Das, Ben Berkhout, Neil Almond, Martin P Cranage
In order to evaluate the role of persisting virus replication during occult phase immunisation in the live attenuated SIV vaccine model, a novel SIVmac239Δnef variant (SIVrtTA) genetically engineered to replicate in the presence of doxycycline was evaluated for its ability to protect against wild-type SIVmac239. Indian rhesus macaques were vaccinated either with SIVrtTA or with SIVmac239Δnef. Doxycycline was withdrawn from 4 of 8 SIVrtTA vaccinates before challenge with wild-type virus. Unvaccinated challenge controls exhibited ~107 peak plasma viral RNA copies/ml persisting beyond the acute phase...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27999434/adoptive-cellular-immunotherapy-for-virus-associated-cancers-a-new-paradigm-in-personalized-medicine
#20
REVIEW
Corey Smith, Rajiv Khanna
Persistent viral infections are associated with the majority of human cancers where infectious agents have been recognized as the primary etiological agent. These viruses contribute to the malignant transformation of human cells either through the expression of oncogenic proteins or chronic inflammation. In spite of the high prevalence of these viral infections in humans, only a small proportion of these individuals who may have an underlying immune defect develop malignant disease. Furthermore, many of these viruses have evolved unique mechanisms to avoid the host immune system to successfully establish latent infection with limited gene expression...
December 21, 2016: Immunology and Cell Biology
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