196 research outputs found
Characterizing Van Kampen Squares via Descent Data
Categories in which cocones satisfy certain exactness conditions w.r.t.
pullbacks are subject to current research activities in theoretical computer
science. Usually, exactness is expressed in terms of properties of the pullback
functor associated with the cocone. Even in the case of non-exactness,
researchers in model semantics and rewriting theory inquire an elementary
characterization of the image of this functor. In this paper we will
investigate this question in the special case where the cocone is a cospan,
i.e. part of a Van Kampen square. The use of Descent Data as the dominant
categorical tool yields two main results: A simple condition which
characterizes the reachable part of the above mentioned functor in terms of
liftings of involved equivalence relations and (as a consequence) a necessary
and sufficient condition for a pushout to be a Van Kampen square formulated in
a purely algebraic manner.Comment: In Proceedings ACCAT 2012, arXiv:1208.430
Viral Load and Cell Tropism During Early Latent Equid Herpesvirus 1 Infection Differ Over Time in Lymphoid and Neural Tissue Samples From Experimentally Infected Horses
Upper respiratory tract infections with Equid Herpesvirus 1 (EHV-1) typically result in a peripheral blood mononuclear cell-associated viremia, which can lead to vasculopathy in the central nervous system. Primary EHV-1 infection also likely establishes latency in trigeminal ganglia (TG) via retrograde axonal transport and in respiratory tract-associated lymphatic tissue. However, latency establishment and reactivation are poorly understood. To characterize the pathogenesis of EHV-1 latency establishment and maintenance, two separate groups of yearling horses were experimentally infected intranasally with EHV-1, strain Ab4, and euthanized 30 days post infection (dpi), (n = 9) and 70 dpi (n = 6). During necropsy, TG, sympathetic trunk (ST), retropharyngeal and mesenteric lymph nodes (RLn, MesLn) and kidney samples were collected. Viral DNA was detected by quantitative PCR (qPCR) in TG, ST, RLn, and MesLn samples in horses 30 and 70 dpi. The number of positive TG, RLn and MesLn samples was reduced when comparing horses 30 and 70 dpi and the viral copy number in TG and RLn significantly declined from 30 to 70 dpi. EHV-1 late gene glycoprotein B reverse transcriptase PCR and IHC results for viral protein were consistently negative, thus lytic replication was excluded in the present study. Mild inflammation could be detected in all neural tissue samples and inflammatory infiltrates mainly consisted of CD3+ T-lymphocytes (T-cells), frequently localized in close proximity to neuronal cell bodies. To identify latently infected cell types, in situ hybridization (ISH, RNAScope®) detecting viral DNA was used on selected qPCR- positive neural tissue sections. In ganglia 30 dpi, EHV-1 ISH signal was located in the neurons of TG and ST, but also in non-neuronal support or interstitial cells surrounding the neuron. In contrast, distinct EHV-1 signal could only be observed in neurons of TG 70 dpi. Overall, detection of latent EHV-1 in abdominal tissue samples and non-neuronal cell localization suggests, that EHV-1 uses T-cells during viremia as alternative route toward latency locations in addition to retrograde neuronal transport. We therefore hypothesize that EHV-1 follows the same latency pathways as its close relative human pathogen Varicella Zoster Virus
Evaluation of immune responses following infection of ponies with an EHV-1 ORF1/2 deletion mutant
Equine herpesvirus-1 (EHV-1) infection remains a significant problem despite
the widespread use of vaccines. The inability to generate a protective immune
response to EHV-1 vaccination or infection is thought to be due to
immunomodulatory properties of the virus, and the ORF1 and ORF2 gene products
have been hypothesized as potential candidates with immunoregulatory
properties. A pony infection study was performed to define immune responses to
EHV-1, and to determine if an EHV-1 ORF1/2 deletion mutant (ΔORF1/2) would
have different disease and immunoregulatory effects compared to wild type
EHV-1 (WT). Infection with either virus led to cytokine responses that
coincided with the course of clinical disease, particularly the biphasic
pyrexia, which correlates with respiratory disease and viremia, respectively.
Similarly, both viruses caused suppression of proliferative T-cell responses
on day 7 post infection (pi). The ΔORF1/ORF2 virus caused significantly
shorter primary pyrexia and significantly reduced nasal shedding, and an
attenuated decrease in PBMC IL-8 as well as increased Tbet responses compared
to WT-infected ponies. In conclusion, our findings are (i) that infection of
ponies with EHV-1 leads to modulation of immune responses, which are
correlated with disease pathogenesis, and (ii) that the ORF1/2 genes are of
importance for disease outcome and modulation of cytokine responses
- …