9 research outputs found
Prior dengue virus exposure shapes T Cell immunity to Zika Virus in humans
While progress has been made in characterizing humoral immunity to Zika virus (ZIKV) in humans, little is known regarding the corresponding T cell responses to ZIKV. Here we investigate the kinetics and viral epitopes targeted by T cells responding to ZIKV and address the critical question of whether pre-existing dengue virus (DENV) T cell immunity modulates these responses. We find that memory T cell responses elicited by prior infection with DENV or vaccination with Tetravalent Dengue Attenuated Vaccines (TDLAV) recognize ZIKV-derived peptides. This cross-reactivity is explained by the sequence similarity of the two viruses, as the ZIKV peptides recognized by DENV-elicited memory T cells are identical or highly conserved in DENV and ZIKV. DENV exposure prior to ZIKV infection also influences the timing and magnitude of the T cell response. ZIKV-reactive T cells in the acute phase of infection are detected earlier and in greater magnitude in DENV-immune patients. Conversely, the frequency of ZIKV-reactive T cells continues to rise in the convalescent phase in DENV-naive donors, but declines in DENV pre-exposed donors, compatible with more efficient control of ZIKV replication and/or clearance of ZIKV antigen. The quality of responses is also influenced by previous DENV exposure, and ZIKV-specific CD8 T cells form DENV pre-exposed donors selectively up-regulated granzyme B and PD1, as compared to DENV-naïve donors. Finally, we discovered that ZIKV structural proteins (E, prM and C) are major targets of both the CD4 and CD8 T cell responses, whereas DENV T cell epitopes are found primarily in nonstructural proteins
Role of oxidative damage in the pathogenesis of viral infections of the nervous system
Oxidative stress, primarily due to increased
generation of reactive oxygen species (ROS) and
reactive nitrogen species (RNS), is a feature of many
viral infections. ROS and RNS modulate the
permissiveness of cells to viral replication, regulate host
inflammatory and immune responses, and cause
oxidative damage to both host tissue and progeny virus.
The lipid-rich nervous system is particularly susceptible
to lipid peroxidation, an autocatalytic process that
damages lipid-containing structures and yields reactive
by-products, which can covalently modify and damage
cellular macromolecules. Oxidative injury is a
component of acute encephalitis caused by herpes
simplex virus type 1 and reovirus, neurodegenerative
disease caused by human immunodeficiency virus and
murine leukemia virus, and subacute sclerosing
panencephalitis caused by measles virus. The extent to
which oxidative damage plays a beneficial role for the
host by limiting viral replication is largely unknown. An
enhanced understanding of the role of oxidative damage
in viral infections of the nervous system may lead to
therapeutic strategies to reduce tissue damage during
viral infection without impeding the host antiviral
response
What is the price of science?
The peer-reviewed scientific literature is the bedrock of science. However, scientific publishing is undergoing dramatic changes, which include the expansion of open access, an increased number of for-profit publication houses, and ready availabil-ity of preprint manuscripts that have not been peer reviewed. In this opinion article, we discuss the inequities and concerns that these changes have wrought. © 2021 Alwine et al.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]
Reovirus infection triggers inflammatory responses to dietary antigens and development of celiac disease
Viral infections have been proposed to elicit pathological processes leading to the initiation of T helper 1 (TH1) immunity against dietary gluten and celiac disease (CeD). To test this hypothesis and gain insights into mechanisms underlying virus-induced loss of tolerance to dietary antigens, we developed a viral infection model that makes use of two reovirus strains that infect the intestine but differ in their immunopathological outcomes. Reovirus is an avirulent pathogen that elicits protective immunity, but we discovered that it can nonetheless disrupt intestinal immune homeostasis at inductive and effector sites of oral tolerance by suppressing peripheral regulatory T cell (pTreg) conversion and promoting TH1 immunity to dietary antigen. Initiation of TH1 immunity to dietary antigen was dependent on interferon regulatory factor 1 and dissociated from suppression of pTreg conversion, which was mediated by type-1 interferon. Last, our study in humans supports a role for infection with reovirus, a seemingly innocuous virus, in triggering the development of CeD