Summer can be the slow season of research with labs taking the time to enjoy the Seattle sunshine and take those long overdue vacations. The publication list from CERID labs, PIs, and lab technicians say otherwise – 8 publications have hit the PubMed stands since the second week of August. The scope of the individual publications is wide, covering a number of important pathogens and viruses from diarrheal Cryptosporidium parvum to neuropathological West Nile virus infections. Read on for highlights from the abstract, links for more information on each lab, and the diseases studied in this month’s publication round up! Publications are listed by the date published. All descriptions of the work have been paraphrased from the publications' respective abstracts and are cited as such.
Merkel cell carcinoma (MCC) is an extremely aggresive skin cancer caused by Merkel cell polyomavirus (MCPyV) oncoproteins in the majority of cases (80%). Exploiting the fact that these oncoproteins are present in most patients with MCC, therein making it relatively and uniquely easy to pinpoint, characterize and augmnent tumor-specific CD4+ T cells, the Koelle lab and their collaborators report the identification of the CD4+ T-cell responses against six MCPyV epitopes. One of the epitopes was found is be a conserved, essential viral oncogenic domain that inhibits the cellular retinoblastoma (Rb) tumor suppressor. The publication pulls together the work of UW Departments of Medicine, Pathology, and Dermatology as well as the Translational Research Program at the Benaroya Research Institute at Virginia Mason. Read the full abstract and author list here!
RIG-I-Like Receptors (RLRs) are vital pathogen recognition receptors in the defense against RNA viruses like West Nile Virus (WNV), a virus that continues to grow and spread within the US. By employing a systems biology approach, the publication defines the contributions of each RLR in the innate immune response to WNV. Analyses reveal the RLR-driven signature of macrophage polarization, innate immune protection, and immune programming against WNV infection. All authors are associated with the UW Department of Immunology and Center for Innate Immunity and Immune Disease. Read the full abstract and author list here!
Zika virus (ZIKV) infection during pregnancy causes congenital abnormalities, including microcephaly. However, rates vary widely, and the contributing risk factors remain unclear. The Gale lab, and 30 other contributing author departments globally, examined the serum antibody response to ZIKV and other flaviviruses in Brazilian women giving birth during the 2015-2016 outbreak. Infected pregnancies with intermediate or higher ZIKV antibody enhancement titers were at increased risk to give birth to microcephalic infants compared with those with lower titers and analysis of ZIKV-infected pregnant macaques revealed that fetal brain damage was more frequent in mothers with higher enhancement titers. Thus, features of the maternal antibodies are associated with and may contribute to the genesis of ZIKV-associated microcephaly. Read the full paper and author list here!
West Nile virus (WNV) infections are acutely controlled by innate immunity in peripheral tissues outside of the central nervous system (CNS) but WNV can evade the actions of interferon (IFN) to facilitate CNS invasion, causing encephalitis, encephalomyelitis, and death. Recent studies indicate that STimulator of INterferon Gene (STING), canonically known for initiating a type I IFN production and innate immune response to cytosolic DNA, is required for host defense against neurotropic RNA viruses. The Gale lab in collaboration with UW Departments of Global Health, Immunology, and Comparative Medicine, the Department of Defense, Fred Hutchinson Cancer Research Center and Rutgers University evaluated the role of STING in host defense to control WNV infection and pathology in a murine model of infection. Read the full abstract and author list here!
Cryptosporidium is among the most common causes of severe diarrhea in African children 0-23 months old. It is associated with excess mortality, stunting and malnutrition. The most common manifestation of cryptosporidium is intestinal diarrheal disease. However, respiratory cryptosporidiosis has been documented in up to a third of children presenting with diarrhea. It is unclear whether respiratory involvement is a transient phenomenon or a reservoir for gastrointestinal (GI) disease. The Van Voorhis lab, Malawi-Liverpool Wellcome Trust Clinical Research Programme, University of Malawi, and the Liverpool School of Tropical Medicine collaborate to evaluate the role of respiratory cryptosporidiosis in pediatric diarrheal disease. Read the full abstract and author list here!
Vibrio cholerae infection provides long-lasting protective immunity, while oral, inactivated cholera vaccines (OCV) result in more-limited protection. To identify characteristics of the innate immune response that may distinguish natural V. cholerae infection from OCV, we stimulated differentiated, macrophage-like THP-1 cells with live versus heat-inactivated V. cholerae with and without endogenous or exogenous cholera holotoxin (CT). Based on the Weil lab's findings, in collaboration with Harvard Departments of Medicine, Microbiology, Immunology and Infectious Disease, and Pediartics, Massachusetts General Hospital for Children and the International Center for Diarrheal Disease and Research in Bangladesh, the stimulation of IL-23 production may be a determinant of protective immunity following V. cholerae infection. Read the full abstract and author list here!
Hollow fiber technology is a powerful tool for the culture of difficult-to-grow cells. Cryptosporidium parvum has a multistage sexual and asexual life cycle that has proved difficult to culture by conventional in vitro culture methods. Here, the Arnold lab, Van Voorhis lab and collaborators at Pace University describe a method utilizing a hollow fiber bioreactor for the continuous in vitro growth of C. parvum that produces sexual and asexual stages. The method enables the evaluation of potential therapeutic compounds under conditions that mirror the dynamic conditions found in the gut facilitating preliminary pharmacokinetic and pharmacodynamic data to be obtained. Read the full paper and author list here!
Legionella pneumophila (Lp) is a flagellated, intracellular bacterium that can cause Legionnaires' disease (LD). Lp activates multiple innate immune receptors, and TOLLIP dampens MyD88-dependent signaling and may influence susceptibility to LD. The Shah and Hawn labs, with collaborators at the Veterans Affairs Puget Sound Health Care System, the University of Amsterdam, and the Eramus Medical Center in the Netherlands, evaluated the effect of TOLLIP on innate immunity, pneumonia severity, and LD susceptibility in mouse lungs and human populations. Read the full abstract and author list here!
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