Contributions of CD8 T cells to the pathogenesis of mouse adenovirus type 1 respiratory infection

Molloy, Caitlyn T.; Andonian, Jennifer; Seltzer, Harrison M; Procario, Megan C.; Watson, Michael; Weinberg, Jason B.

doi:10.1016/j.virol.2017.04.005

Cited by 16 publications

(14 citation statements)

References 60 publications

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“…Effects of immunoproteasome deficiency on MAV-1 replication in lungs of adult mice. CD8 T cells contribute to clearance of MAV-1 from the lungs of infected mice (8). Activity of the immunoproteasome, which aids in proteolytic processing of proteins into peptides that are presented by MHC class I to CD8 T cells (2,11), increases in the lungs of mice during acute infection with MAV-1 (9), suggesting that the immunoproteasome plays an essential role in host defense against MAV-1.…”

Section: Resultsmentioning

confidence: 99%

“…Proteasome and immunoproteasome activity contribute to the processing of proteins to generate peptides presented to CD8 T cells by MHC class I (2). CD8 T cells are essential for efficient clearance of MAV-1 from the lungs (8). We have therefore determined the extent to which immunoproteasome activity is required for CD8 T cell-mediated virus clearance.…”

Section: Discussionmentioning

confidence: 99%

“…For instance, expression of IFN-␥ and proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-␣) and interleukin-1␤ (IL-1␤), increases in the lungs during MAV-1 respiratory infection (6,7). CD8 T cells contribute to MAV-1 clearance from the lungs and promote MAV-1-induced pulmonary inflammation (8). We demonstrated that MAV-1 infection upregulates the expression of immunoproteasome subunits and increases immunoproteasome activity in hearts and lungs in an IFN-␥-dependent manner (9).…”

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confidence: 99%

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Age-Dependent Effects of Immunoproteasome Deficiency on Mouse Adenovirus Type 1 Pathogenesis

Chandrasekaran

Adkins

Seltzer

et al. 2019

J Virol

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Acute respiratory infection with mouse adenovirus type 1 (MAV-1) induces activity of the immunoproteasome, an inducible form of the proteasome that shapes CD8 T cell responses by enhancing peptide presentation by major histocompatibility complex (MHC) class I. We used mice deficient in all three immunoproteasome subunits (triple-knockout [TKO] mice) to determine whether immunoproteasome activity is essential for control of MAV-1 replication or inflammatory responses to acute infection. Complete immunoproteasome deficiency in adult TKO mice had no effect on MAV-1 replication, virus-induced lung inflammation, or adaptive immunity compared to C57BL/6 (B6) controls. In contrast, immunoproteasome deficiency in neonatal TKO mice was associated with decreased survival and decreased lung gamma interferon (IFN-γ) expression compared to B6 controls, although without substantial effects on viral replication, histological evidence of inflammation, or expression of the proinflammatory cytokines tumor necrosis factor alpha and interleukin-1β in lungs or other organs. T cell recruitment and IFN-γ production was similar in lungs of infected B6 and TKO mice. In lungs of uninfected B6 mice, we detected low levels of immunoproteasome subunit mRNA and protein that increased with age. Immunoproteasome subunit expression was lower in lungs of adult IFN-γ-deficient mice compared to B6 controls. Together, these results demonstrate developmental regulation of the immunoproteasome that is associated with age-dependent differences in MAV-1 pathogenesis. IMPORTANCE MAV-1 infection is a useful model to study the pathogenesis of an adenovirus in its natural host. Host factors that control MAV-1 replication and contribute to inflammation and disease are not fully understood. The immunoproteasome is an inducible component of the ubiquitin proteasome system that shapes the repertoire of peptides presented by MHC class I to CD8 T cells, influences other aspects of T cell survival and activation, and promotes production of proinflammatory cytokines. We found that immunoproteasome activity is dispensable in adult mice. However, immunoproteasome deficiency in neonatal mice increased mortality and impaired IFN-γ responses in the lungs. Baseline immunoproteasome subunit expression in lungs of uninfected mice increased with age. Our findings suggest the existence of developmental regulation of the immunoproteasome, like other aspects of host immune function, and indicate that immunoproteasome activity is a critical protective factor early in life.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Age-Dependent Effects of Immunoproteasome Deficiency on Mouse Adenovirus Type 1 Pathogenesis

Chandrasekaran

Adkins

Seltzer

et al. 2019

J Virol

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“…Studies with immunodeficient mice have shown that T cells are required for long‐term survival of infection and contribute to immunopathology during the acute phase of infection . CD8 T cells, but not CD4 T cells, are required for efficient clearance of MAdV‐1 from the lungs and for virus‐induced inflammation and weight loss . These effects of CD8 T cells are not mediated exclusively by IFN‐γ, perforin, or Fas/FasL .…”

Section: Madv‐1 Pathogenesis—tropism Adaptive Immune Responsesmentioning

confidence: 99%

“…CD8 T cells, but not CD4 T cells, are required for efficient clearance of MAdV‐1 from the lungs and for virus‐induced inflammation and weight loss . These effects of CD8 T cells are not mediated exclusively by IFN‐γ, perforin, or Fas/FasL . MAdV‐1‐induced humoral responses have been studied in outbred and inbred mice.…”

Section: Madv‐1 Pathogenesis—tropism Adaptive Immune Responsesmentioning

confidence: 99%

Murine adenoviruses: tools for studying adenovirus pathogenesis in a natural host

Hemmi

Spindler

2019

FEBS Letters

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Small laboratory animals are powerful models for investigating in vivo viral pathogenesis of a number of viruses. For adenoviruses (AdVs), however, species-specificity poses limitations to studying human adenoviruses (HAdVs) in mice and other small laboratory animals. Thus, this review covers work on naturally occurring mouse AdVs, primarily mouse adenovirus type 1 (MAdV-1), a member of the species Murine mastadenovirus A. Molecular genetics, virus life cycle, cell and tissue tropism, interactions with the host immune response, persistence, and host genetics of susceptibility are described. A brief discussion of MAdV-2 (member of species Murine mastadenovirus B) and MAdV-3 (member of species Murine mastadenovirus C) is included. We report the use of MAdVs in the development of vectors and vaccines.

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Animal Adenoviruses

Gaba¹,

Ayalew²,

Tikoo³

2019

Recent Advances in Animal Virology

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Contributions of CD8 T cells to the pathogenesis of mouse adenovirus type 1 respiratory infection

Cited by 16 publications

References 60 publications

Age-Dependent Effects of Immunoproteasome Deficiency on Mouse Adenovirus Type 1 Pathogenesis

Age-Dependent Effects of Immunoproteasome Deficiency on Mouse Adenovirus Type 1 Pathogenesis

Murine adenoviruses: tools for studying adenovirus pathogenesis in a natural host

Animal Adenoviruses

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