Dataset Information

STAT1-independent control of a neurotropic measles virus challenge in primary neurons and infected mice.

ABSTRACT: Neurons are chiefly nonrenewable; thus, cytolytic immune strategies to clear or control neurotropic viral infections could have lasting neurologic consequences. IFN-? is a potent antiviral cytokine that is critical for noncytolytic clearance of multiple neurotropic viral infections, including measles virus (MV); however, the downstream pathways through which IFN-? functions in neurons have not been defined. Unlike most cell types studied to date in which IFN-? affects gene expression via rapid and robust activation of STAT1, basal STAT1 levels in primary hippocampal neurons are constitutively low, resulting in attenuated STAT1 activation and consequently slower kinetics of IFN-?-driven STAT1-dependent gene expression. Given this altered expression and activation of STAT1 in neurons, we sought to determine whether STAT1 was required for IFN-?-mediated protection from infection in neurons. To do so, we evaluated the consequences of MV challenge of STAT1-deficient mice and primary hippocampal neurons explanted from these mice. Surprisingly, the absence of STAT1 did not restrict the ability of IFN-? to control viral infection either in vivo or ex vivo. Moreover, the canonical IFN-?-triggered STAT1 gene expression profile was not induced in STAT1-deficient neurons, suggesting that IFN-? regulates neuronal STAT1-independent pathways to control viral replication.

SUBMITTER: O'Donnell LA

PROVIDER: S-EPMC3273675 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

STAT1-independent control of a neurotropic measles virus challenge in primary neurons and infected mice.

O'Donnell Lauren A LA Conway Stephen S Rose R Wesley RW Nicolas Emmanuelle E Slifker Michael M Balachandran Siddharth S Rall Glenn F GF

Journal of immunology (Baltimore, Md. : 1950) 20120113 4

Neurons are chiefly nonrenewable; thus, cytolytic immune strategies to clear or control neurotropic viral infections could have lasting neurologic consequences. IFN-γ is a potent antiviral cytokine that is critical for noncytolytic clearance of multiple neurotropic viral infections, including measles virus (MV); however, the downstream pathways through which IFN-γ functions in neurons have not been defined. Unlike most cell types studied to date in which IFN-γ affects gene expression via rapid a ...[more]

PMID: 22246627

Similar Datasets

Project description:Monkeypox virus (MPXV) is the etiological agent of human (MPX). It is an emerging orthopoxvirus zoonosis in the tropical rain forest of Africa and is endemic in the Congo-basin and sporadic in West Africa; it remains a tropical neglected disease of persons in impoverished rural areas. Interaction of the human population with wildlife increases human infection with MPX virus (MPXV), and infection from human to human is possible. Smallpox vaccination provides good cross-protection against MPX; however, the vaccination campaign ended in Africa in 1980, meaning that a large proportion of the population is currently unprotected against MPXV infection. Disease control hinges on deterring zoonotic exposure to the virus and, barring that, interrupting person-to-person spread. However, there are no FDA-approved therapies against MPX, and current vaccines are limited due to safety concerns. For this reason, new studies on pathogenesis, prophylaxis and therapeutics are still of great interest, not only for the scientific community but also for the governments concerned that MPXV could be used as a bioterror agent. In the present study, a new vaccination strategy approach based on three recombinant bovine herpesvirus 4 (BoHV-4) vectors, each expressing different MPXV glycoproteins, A29L, M1R and B6R were investigated in terms of protection from a lethal MPXV challenge in STAT1 knockout mice. BoHV-4-A-CMV-A29LgD106?TK, BoHV-4-A-EF1?-M1RgD106?TK and BoHV-4-A-EF1?-B6RgD106?TK were successfully constructed by recombineering, and their capacity to express their transgene was demonstrated. A small challenge study was performed, and all three recombinant BoHV-4 appeared safe (no weight-loss or obvious adverse events) following intraperitoneal administration. Further, BoHV-4-A-EF1?-M1RgD106?TK alone or in combination with BoHV-4-A-CMV-A29LgD106?TK and BoHV-4-A-EF1?-B6RgD106?TK, was shown to be able to protect, 100% alone and 80% in combination, STAT1(-/-) mice against mortality and morbidity. This work demonstrated the efficacy of BoHV-4 based vectors and the use of BoHV-4 as a vaccine-vector platform.

Dataset Information

STAT1-independent control of a neurotropic measles virus challenge in primary neurons and infected mice.

Publications

STAT1-independent control of a neurotropic measles virus challenge in primary neurons and infected mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets