Autophagy Genes Enhance Murine Gammaherpesvirus 68 Reactivation from Latency by Preventing Virus-Induced Systemic Inflammation

Park, Sunmin; Buck, Michael D.; Desai, Chandni; Zhang, Xin; Loginicheva, Ekaterina; Martinez, Jennifer; Freeman, Michael L.; Saitoh, Tatsuya; Akira, Shizuo; Guan, Jun; He, You Wen; Blackman, Marcia A.; Handley, Scott A.; Levine, Beth; Green, Douglas R.; Reese, Tiffany A.; Artyomov, Maxim N.; Virgin, Herbert W.

doi:10.1016/j.chom.2015.12.010

Cited by 56 publications

(64 citation statements)

References 86 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Mice were latently infected with the γ-herpesvirus MHV68 and the ability of MHV68 to reactivate from PECs was evaluated (36,37). We found no difference in viral reactivation from latently infected LysMD3 WT or LysMD3-deficient PECs ( Figure 7B and Figure 7C).…”

Section: Lack Of a Role For Mlysmd3 In Response To Viral Infectionmentioning

confidence: 88%

“…MHV68 WUMS (ATCC VR1465) was used and reactivation from latency was measured as described (36,37,77). Mice were infected with 1e6 PFU MHV68 IP and after 16 days, PECs or spleens were pooled from 3-5 mice and serial dilutions of cells were plated on a MEF monolayer.…”

Section: Lps Treatmentsmentioning

confidence: 99%

“…RNA sequencing RNA from the distal ileum was purified, an Illumina sequencing library was generated, and libraries sequenced (HiSeq platform), as described (37). Five to six mice were included in each group.…”

Section: S Rrna Illumina Sequencing and Analysismentioning

confidence: 99%

See 2 more Smart Citations

LysMD3 is a type II membrane protein without an role in the response to a range of pathogens

Yokoyama

Baldridge

Leung

et al. 2018

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Section: Lack Of a Role For Mlysmd3 In Response To Viral Infectionmentioning

confidence: 88%

Section: Lps Treatmentsmentioning

confidence: 99%

See 1 more Smart Citation

LysMD3 is a type II membrane protein without an role in the response to a range of pathogens

Yokoyama

Baldridge

Leung

et al. 2018

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

“…Atgs exert a concerted effect in autophagy, i.e., autophagosome initiation and elongation and lysosomal functions (28). Various Atgs play diverse roles in innate and inflammatory responses, such as the eradication of intracellular pathogens, murine gammaherpesvirus 68 reactivation from latency, Ag presentation, and innate immune signaling in a cell type-specific manner (28,35,36). Despite these findings, research on the molecular mechanisms of Atg regulation in macrophages during infection is in its infancy.…”

Section: Discussionmentioning

confidence: 99%

PPAR-α Activation Mediates Innate Host Defense through Induction of TFEB and Lipid Catabolism

Kim

Lee

Kim

et al. 2017

The Journal of Immunology

131

155

View full text Add to dashboard Cite

The role of peroxisome proliferator–activated receptor α (PPAR-α) in innate host defense is largely unknown. In this study, we show that PPAR-α is essential for antimycobacterial responses via activation of transcription factor EB (TFEB) transcription and inhibition of lipid body formation. PPAR-α deficiency resulted in an increased bacterial load and exaggerated inflammatory responses during mycobacterial infection. PPAR-α agonists promoted autophagy, lysosomal biogenesis, phagosomal maturation, and antimicrobial defense against Mycobacterium tuberculosis or M. bovis bacillus Calmette–Guérin. PPAR-α agonists regulated multiple genes involved in autophagy and lysosomal biogenesis, including Lamp2, Rab7, and Tfeb in bone marrow–derived macrophages. Silencing of TFEB reduced phagosomal maturation and antimicrobial responses, but increased macrophage inflammatory responses during mycobacterial infection. Moreover, PPAR-α activation promoted lipid catabolism and fatty acid β-oxidation in macrophages during mycobacterial infection. Taken together, our data indicate that PPAR-α mediates antimicrobial responses to mycobacterial infection by inducing TFEB and lipid catabolism.

show abstract

“…Autophagy is an essential cellular process whereby cytoplasmic cargo, and sometimes a pathogen, is engulfed in a double-membranebound vesicle, termed the autophagosome, that fuses to the lysosome for degradation. We recently reported that multiple Atg genes in myeloid cells regulate systemic inflammation, and especially IFN-␥, thus inhibiting viral reactivation (17). In the absence of Atg genes, MHV68 fails to reactivate efficiently, and neutralization of IFN-␥ partially reverses this defect.…”

Section: Systemic Inflammation and Reactivationmentioning

confidence: 99%

Coinfections: Another Variable in the Herpesvirus Latency-Reactivation Dynamic

Reese

2016

J Virol

View full text Add to dashboard Cite

Chronic viruses, such as herpesviruses, shape host physiology. These viruses modulate the inflammatory state of the immune system and have evolved to harness inflammation as a mechanism to regulate viral latency and reactivation. In this review, I examine some of the recent work demonstrating the important role of inflammation in the regulation of the herpesvirus life cycle and discuss recent work that implicates coinfection in the regulation of herpesvirus latency. Herpesviruses are a family of viruses that have closely evolved with their host species. Every vertebrate examined has at least one herpesvirus, and each herpesvirus is closely associated with one host species (1). In humans, more than 90% of the population is infected with at least one herpesvirus (2). This suggests that these viruses have evolved with their hosts over a long period of time and are well adapted to them. It also suggests that our immune systems have evolved in the company of these infections and are shaped by their durable presence.Herpesviruses establish lifelong chronic infections with periods of limited viral gene expression and no viral progeny production. This noncytopathic infection is termed latency. In the case of gammaherpesviruses, which are the focus of this review, latency is established primarily in B cells but also in macrophages and dendritic cells (1).Rather than being a static event, latency is quite dynamic. Even though chronic infection is usually associated with little to no disease, these viruses are undergoing brief periods of reactivation during which small amounts of virus are produced. Production of virus during latency is likely important for spread of the virus to new hosts, as well as maintenance of a viral reservoir in the host. However, these reactivation events are tightly controlled by the immune system, which forces the virus to return to latency. Both the delicate balance between viral reactivation and latency and the complex relationship between the host immune system and herpesviruses are important for understanding how viruses influence host physiology.We recently demonstrated not only that a mouse gammaherpesvirus (murine gammaherpesvirus 68 [MHV68; also known as ␥HV68 or MHV4]) modulates the immune system but also that subsequent infections with particular pathogens induce gammaherpesvirus reactivation from latency (3). These findings add another layer of complexity to our understanding of host-virus interactions and suggest that this relationship is modulated by coinfections. This has important implications for how herpesviruses shape immunity.

show abstract

Autophagy Genes Enhance Murine Gammaherpesvirus 68 Reactivation from Latency by Preventing Virus-Induced Systemic Inflammation

Cited by 56 publications

References 86 publications

LysMD3 is a type II membrane protein without an role in the response to a range of pathogens

LysMD3 is a type II membrane protein without an role in the response to a range of pathogens

PPAR-α Activation Mediates Innate Host Defense through Induction of TFEB and Lipid Catabolism

Coinfections: Another Variable in the Herpesvirus Latency-Reactivation Dynamic

Contact Info

Product

Resources

About