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T-cell immunity against cytomegalovirus in HIV infection and aging: relationships with inflammation, immune activation, and frailty
AbstractBoth aging and treated human immunodeficiency virus (HIV) infection are characterized by low-level chronic inflammation and immune activation which contribute to the development of age-related diseases, frailty, and early mortality. Chronic cytomegalovirus (CMV) infection is highly prevalent in older adults and HIV-infected populations. A number of studies have shown that CMV induces broad and strong T-cell responses in CMV-seropositive older adults and HIV-infected individuals. CMV infection rarely develops into clinical disease in immunocompetent individuals. However, a large body of literature has shown adverse ...
Source: Medical Microbiology and Immunology - March 20, 2019 Category: Microbiology Source Type: research

Generation, maintenance and tissue distribution of T cell responses to human cytomegalovirus in lytic and latent infection
AbstractUnderstanding how the T cell memory response directed towards human cytomegalovirus (HCMV) develops and changes over time while the virus persists is important. Whilst HCMV primary infection and periodic reactivation is well controlled by T cell responses in healthy people, when the immune system is compromised such as post-transplantation, during pregnancy, or underdeveloped such as in new-born infants and children, CMV disease can be a significant problem. In older people, HCMV infection is associated with increased risk of mortality and despite overt disease rarely being seen there are increases in HCMV-DNA in u...
Source: Medical Microbiology and Immunology - March 19, 2019 Category: Microbiology Source Type: research

Innate immune response in patients with acute Zika virus infection
In this study, we evaluated the mRNA expression of innate immune receptors (TLR3, TLR7, TLR8, TLR9, melanoma differentiation-associated protein 5/MDA-5, and reti noic acid inducible gene/RIG-1), its adapter molecules (Myeloid Differentiation Primary Response Gene 88/Myd88,Toll/IL-1 Receptor Domain-Containing Adaptor-Inducing IFN- β/TRIF), and cytokines (IL-6, IL-12, TNF-α, IFN-α, IFN-β, and IFN-γ) in the acute phase of patients infected by ZIKV using real-time PCR in peripheral blood. Patients with acute ZIKV infection had high expression of TLR3, IFN-α, IFN-β, and IFN-γ when compared to healthy controls. In additi...
Source: Medical Microbiology and Immunology - March 15, 2019 Category: Microbiology Source Type: research

Intertwined: SAMHD1 cellular functions, restriction, and viral evasion strategies
AbstractSAMHD1 was initially described for its ability to efficiently restrict HIV-1 replication in myeloid cells and resting CD4+ T cells. However, a growing body of evidence suggests that SAMHD1-mediated restriction is by far not limited to lentiviruses, but seems to be a general concept that applies to most retroviruses and at least a number of DNA viruses. SAMHD1 anti-viral activity was long believed to be solely due to its ability to deplete cellular dNTPs by enzymatic degradation. However, since its discovery, several new functions have been attributed to SAMHD1. It has been demonstrated to bind nucleic acids, to mod...
Source: Medical Microbiology and Immunology - March 15, 2019 Category: Microbiology Source Type: research

Discrimination between recent and non-recent HIV infections using routine diagnostic serological assays
AbstractThe suitability of routine diagnostic HIV assays to accurately discriminate between recent and non-recent HIV infections has not been fully investigated. The aim of this study was to compare an established HIV recency assay, the Sedia limiting antigen HIV avidity assay (LAg), with the diagnostic assays; Abbott ARCHITECT HIV Ag/Ab Combo and INNO-LIA HIV line assays. Samples from all new HIV diagnoses in Ireland from January to December 2016 (n = 455) were tested. An extended logistic regression model, the Spiegelhalter–Knill–Jones method, was utilised to establish a scoring system to predict recency of HIV i...
Source: Medical Microbiology and Immunology - March 10, 2019 Category: Microbiology Source Type: research

Kinetics of Alphatorquevirus plasma DNAemia at late times after allogeneic hematopoietic stem cell transplantation
AbstractTorque teno virus (TTV) plasma DNA load has been consistently shown to be a surrogate biomarker of immunosuppression in solid organ transplant recipients. It is uncertain whether it may behave similarly in allogeneic hematopoietic stem cell transplant recipients (allo-HSCT). Here, we characterized the dynamics of TTV DNAemia in patients undergoing T-cell replete allo-SCT at late times after transplantation (>  day + 100). This retrospective single-center observational study included 33 allo-HSCT patients. Plasma TTV DNA loads were quantified by real-time PCR before initiating the conditioning regimen and a...
Source: Medical Microbiology and Immunology - March 8, 2019 Category: Microbiology Source Type: research

Fuel and brake of memory T cell inflation
AbstractMemory T cell inflation is a process in which a large number of effector memory T cells accumulates in peripheral tissues. This phenomenon is observed upon certain low level persistent virus infections, but it is most commonly described upon infection with the β-herpesvirus Cytomegalovirus. Due to the induction of this large pool of functional effector CD8 T cells in peripheral tissues, the interest in using CMV-based vaccine vectors for vaccination purposes is rising. However, the exact mechanisms of memory T cell inflation are not yet fully understood. It is clear that repetitive exposure to antigen is a key det...
Source: Medical Microbiology and Immunology - March 8, 2019 Category: Microbiology Source Type: research

High polymorphism rates in well-known T cell epitopes restricted by protective HLA alleles during HIV infection are associated with rapid disease progression in early-infected MSM in China
AbstractT cell epitopes restricted by several protective HLA alleles, such as B*57, B*5801, B*27, B*51 and B*13, have been very well defined over the past two decades. We investigated 32 well-known T cell epitopes restricted by protective HLA molecules among 54 Chinese men who have sex with men (MSM) at the early stage of HIV-1 infection. Subjects in our cohort carrying protective HLA types did not exhibit slow CD4 T cell count decline (P = 0.489) or low viral load set points (P = 0.500). Variations occurred in 96.88% (31/32) of the known wild-type epitopes (rate 1.85–100%), and the variation rates of the strains...
Source: Medical Microbiology and Immunology - March 7, 2019 Category: Microbiology Source Type: research

Persistent viral replication and the development of T-cell responses after intranasal infection by MCMV
AbstractNatural transmission of cytomegalovirus (CMV) has been difficult to observe. However, recent work using the mouse model of murine (M)CMV demonstrated that MCMV initially infects the nasal mucosa after transmission from mothers to pups. We found that intranasal (i.n.) inoculation of C57BL/6J mice resulted in reliable recovery of replicating virus from the nasal mucosa as assessed by plaque assay. After i.n. inoculation, CD8+ T-cell priming occurred in the mandibular, deep-cervical, and mediastinal lymph nodes within 3  days of infection. Although i.n. infection induced “memory inflation” of T cells specific for...
Source: Medical Microbiology and Immunology - March 7, 2019 Category: Microbiology Source Type: research

Genetic variation and function of the HIV-1 Tat protein
AbstractHuman immunodeficiency virus type 1 (HIV-1) encodes a transactivator of transcription (Tat) protein, which has several functions that promote viral replication, pathogenesis, and disease. Amino acid variation within Tat has been observed to alter the functional properties of Tat and, depending on the HIV-1 subtype, may produce Tat phenotypes differing from viruses ’ representative of each subtype and commonly used in in vivo and in vitro experimentation. The molecular properties of Tat allow for distinctive functional activities to be determined such as the subcellular localization and other intracellular and ext...
Source: Medical Microbiology and Immunology - March 4, 2019 Category: Microbiology Source Type: research

Coevolution pays off: Herpesviruses have the license to escape the DNA sensing pathway
AbstractEarly detection of viral invasion by pattern recognition receptors (PRR) is crucial for the induction of a rapid and efficient immune response. Cytosolic DNA sensors are the most recently described class of PRR, and induce transcription of type I interferons (IFN) and proinflammatory cytokines via the key adaptor protein stimulator of interferon genes (STING). Herpesviruses are a family of large DNA viruses widely known for their immense arsenal of proteins dedicated to manipulating and evading host immune responses. Tantamount to the significant role played by DNA sensors and STING in innate immune responses, herp...
Source: Medical Microbiology and Immunology - February 25, 2019 Category: Microbiology Source Type: research

Conserved peptide vaccine candidates containing multiple Ebola nucleoprotein epitopes display interactions with diverse HLA molecules
AbstractImmunoinformatics has come by leaps and bounds to finding potent vaccine candidates against various pathogens. In the current study, a combination of different T (CD4+ and CD8+) and B cell epitope prediction tools was applied to find peptides containing multiple epitopes against Ebola nucleoprotein (NP) and the presentation of peptides to human leukocyte antigen (HLA) molecules was analyzed by prediction, docking and population coverage tools. Further, potential peptides were analyzed by ELISA for peptide induced IFN- γ secretion in peripheral blood mononuclear cells isolated from healthy volunteers. Six peptides ...
Source: Medical Microbiology and Immunology - February 21, 2019 Category: Microbiology Source Type: research

HCMV latency: what regulates the regulators?
AbstractHuman cytomegalovirus (HCMV) latency and reactivation is regulated by the chromatin structure at the major immediate early promoter (MIEP) within myeloid cells. Both cellular and viral factors are known to control this promoter during latency, here we will review the known mechanisms for MIEP regulation during latency. We will then focus on the virally encoded G-protein coupled receptor, US28, which suppresses the MIEP in early myeloid lineage cells. The importance of this function is underlined by the fact that US28 is essential for HCMV latency in CD34+ progenitor cells and CD14+ monocytes. We will describe cellu...
Source: Medical Microbiology and Immunology - February 14, 2019 Category: Microbiology Source Type: research

Comparison of four adjuvants revealed the  strongest protection against lethal pneumococcal challenge following immunization with PsaA-PspA fusion protein and AS02 as adjuvant
In this study, the fusion protein PsaA-PspA23, together with PspA4, was formulated with four adjuvants Al(OH)3, MF59, AS03, and AS02, and subsequently subjected to dose optimization and immunological evaluation for determination of the antibody titers, bacterial burden, survival rates, and levels of cytokines in mice. All vaccines with high adjuvant doses displayed higher antigen-specific immunoglobulin G (IgG) titers. Bacterial burdens were notably decreased to different extents in the lungs and blood of mice immunized with the antigen and various adjuvants. Among these adjuvants, AS02 provided outstanding protection agai...
Source: Medical Microbiology and Immunology - February 1, 2019 Category: Microbiology Source Type: research

Secretory IgA-mediated immune response in saliva and early detection of Pseudomonas aeruginosa in the lower airways of pediatric cystic fibrosis patients
AbstractPseudomonas aeruginosa (Pa) detection in the paranasal sinuses may help to prevent or postpone bacterial aspiration to the lower airways (LAW) and chronic lung infection in cystic fibrosis (CF). We assessed the ability of an ELISA test for measurement of specificPa secretory IgA (sIgA) in saliva (a potential marker of sinus colonization) to early detect changes in thePa LAW status (indicated by microbiological sputum or cough swab culture and specific serum IgG levels) of 65 patients for three  years, in different investigation scenarios. Increased sIgA levels were detected in saliva up to 22 months before change...
Source: Medical Microbiology and Immunology - January 31, 2019 Category: Microbiology Source Type: research