Conserved allomorphs of MR1 drive the specificity of MR1-restricted TCRs.

Background: Major histocompatibility complex class-1-related protein (MR1), unlike human leukocyte antigen (HLA) class-1, was until recently considered to be monomorphic. MR1 presents metabolites in the context of host responses to bacterial infection. MR1-restricted TCRs specific to tumor cells have been described, raising interest in their potential therapeutic application for cancer treatment.

N-glycosylation of cervicovaginal fluid reflects microbial community, immune activity, and pregnancy status.

Human cervicovaginal fluid (CVF) is a complex, functionally important and glycan rich biological fluid, fundamental in mediating physiological events associated with reproductive health. Using a comprehensive glycomic strategy we reveal an extremely rich and complex N-glycome in CVF of pregnant and non-pregnant women, abundant in paucimannose and high mannose glycans, complex glycans with 2-4 N-Acetyllactosamine (LacNAc) antennae, and Poly-LacNAc glycans decorated with fucosylation and sialylation. N-glycosylation profiles were observed to differ in relation to pregnancy status, microbial composition, immune activation, and pregnancy outcome.

Functional rewiring of G protein-coupled receptor signaling in human labor.

Current strategies to manage preterm labor center around inhibition of uterine myometrial contractions, yet do not improve neonatal outcomes as they do not address activation of inflammation. Here, we identify that during human labor, activated oxytocin receptor (OTR) reprograms the prostaglandin E2 receptor, EP2, in the pregnant myometrium to suppress relaxatory/Gαs-cAMP signaling and promote pro-labor/inflammatory responses via altered coupling of EP2 from Gαq/11 to Gαi/o. The ability of EP2 to signal via Gαi/o is recapitulated with in vitro OT and only following OTR activation, suggesting direct EP2-OTR crosstalk.

Microbial-driven preterm labour involves crosstalk between the innate and adaptive immune response.

There has been a surge in studies implicating a role of vaginal microbiota in spontaneous preterm birth (sPTB), but most are associative without mechanistic insight. Here we show a comprehensive approach to understand the causative factors of preterm birth, based on the integration of longitudinal vaginal microbiota and cervicovaginal fluid (CVF) immunophenotype data collected from 133 women at high-risk of sPTB. We show that vaginal depletion of Lactobacillus species and high bacterial diversity leads to increased mannose binding lectin (MBL), IgM, IgG, C3b, C5, IL-8, IL-6 and IL-1β and to increased risk of sPTB.

Large-scale characterisation of the pregnancy vaginal microbiome and sialidase activity in a low-risk Chinese population.

Vaginal microbiota-host interactions are linked to preterm birth (PTB), which continues to be the primary cause of global childhood mortality. Due to population size, the majority of PTB occurs in Asia, yet there have been few studies of the pregnancy vaginal microbiota in Asian populations. Here, we characterized the vaginal microbiome of 2689 pregnant Chinese women using metataxonomics and in a subset (n = 819), the relationship between vaginal microbiota composition, sialidase activity and leukocyte presence and pregnancy outcomes.

High Viral Diversity and Mixed Infections in Cerebral Spinal Fluid From Cases of Varicella Zoster Virus Encephalitis.

Background: Varicella zoster virus (VZV) may cause encephalitis, both with and without rash. Here we investigate whether viruses recovered from the central nervous system (CNS; encephalitis or meningitis) differ genetically from those recovered from non-CNS samples.

Methods: Enrichment-based deep sequencing of 45 VZV genomes from cerebral spinal fluid (CSF), plasma, bronchoalveolar lavage (BAL), and vesicles was carried out with samples collected from 34 patients with and without VZV infection of the CNS.

Recombination of Globally Circulating Varicella-Zoster Virus.

Unlabelled: Varicella-zoster virus (VZV) is a human herpesvirus, which during primary infection typically causes varicella (chicken pox) and establishes lifelong latency in sensory and autonomic ganglia. Later in life, the virus may reactivate to cause herpes zoster (HZ; also known as shingles). To prevent these diseases, a live-attenuated heterogeneous vaccine preparation, vOka, is used routinely in many countries worldwide.

Rates of vaccine evolution show strong effects of latency: implications for varicella zoster virus epidemiology.

Varicella-zoster virus (VZV) causes chickenpox and shingles, and is found in human populations worldwide. The lack of temporal signal in the diversity of VZV makes substitution rate estimates unreliable, which is a barrier to understanding the context of its global spread. Here, we estimate rates of evolution by studying live attenuated vaccines, which evolved in 22 vaccinated patients for known periods of time, sometimes, but not always undergoing latency.

Evolution of cocirculating varicella-zoster virus genotypes during a chickenpox outbreak in Guinea-Bissau.

Unlabelled: Varicella-zoster virus (VZV), a double-stranded DNA alphaherpesvirus, is associated with seasonal outbreaks of varicella in nonimmunized populations. Little is known about whether these outbreaks are associated with a single or multiple viral genotypes and whether new mutations rapidly accumulate during transmission. Here, we take advantage of a well-characterized population cohort in Guinea-Bissau and produce a unique set of 23 full-length genome sequences, collected over 7 months from eight households.

Deep sequencing of viral genomes provides insight into the evolution and pathogenesis of varicella zoster virus and its vaccine in humans.

Immunization with the vOka vaccine prevents varicella (chickenpox) in children and susceptible adults. The vOka vaccine strain comprises a mixture of genotypes and, despite attenuation, causes rashes in small numbers of recipients. Like wild-type virus, the vaccine establishes latency in neuronal tissue and can later reactivate to cause Herpes zoster (shingles).

Next-generation whole genome sequencing identifies the direction of norovirus transmission in linked patients.

Background: Noroviruses are a highly transmissible and major cause of nosocomial gastroenteritis resulting in bed and hospital-ward closures. Where hospital outbreaks are suspected, it is important to determine the routes of spread so that appropriate infection-control procedures can be implemented. To investigate a cluster of norovirus cases occurring in children undergoing bone marrow transplant, we undertook norovirus genome sequencing by next-generation methods.

Tracking viral evolution during a disease outbreak: the rapid and complete selective sweep of a circovirus in the endangered Echo parakeet.

Circoviruses are among the smallest and simplest of all viruses, but they are relatively poorly characterized. Here, we intensively sampled two sympatric parrot populations from Mauritius over a period of 11 years and screened for the circovirus Beak and feather disease virus (BFDV). During the sampling period, a severe outbreak of psittacine beak and feather disease, which is caused by BFDV, occurred in Echo parakeets.

Patterns of MHC selection in African mole-rats, family Bathyergidae: the effects of sociality and habitat.

African mole-rats are a family of rodents exhibiting an eclectic range of social behaviour and occupying a variety of habitat types. These differences are likely to impact upon the risk of parasite transmission and virulence, with increasing sociality predicted to correspond to an increased risk of transmission. We investigate these factors by analysing the major histocompatibility complex (MHC), a set of genes responsible for encoding highly variable intermediaries of the vertebrate adaptive immune response.