Exosome Biogenesis, Regulation, and Function in Viral Infection

Secreted exosomal microRNAs (miRNAs) mediate interorgan/tissue communications by modulating target gene expression, thereby regulating developmental and physiological functions. However, the source, route, and function in target cells have not been formally established for specific miRNAs. Here, we show that glial miR-274 non-cell-autonomously modulates the growth of synaptic boutons and tracheal branches. Whereas the precursor form of miR-274 is expressed in glia, the mature form of miR-274 distributes broadly, including in synaptic boutons, muscle cells, and tracheal cells. Mature miR-274 is secreted from glia to the circulating hemolymph as an exosomal cargo, a process requiring ESCRT components in exosome biogenesis and Rab11 and Syx1A in exosome release. We further show that miR-274 can function in the neurons or tracheal cells to modulate the growth of synaptic boutons and tracheal branches, respectively. Also, miR-274 uptake into the target cells by AP-2–dependent mechanisms modulates target cell growth. In the target cells, miR-274 down-regulates Sprouty (Sty) through a targeting sequence at the sty 3′ untranslated region, thereby enhancing MAPK signaling and promoting cell growth. miR-274 expressed in glia of an mir-274 null mutant is released as an exosomal cargo in the circulating hemolymph, and such glial-specific expression resets normal levels of Sty and MAPK signaling and modulates target cell growth. mir-274 mutant larvae are hypersensitive to hypoxia, which is suppressed by miR-274 expression in glia or by increasing tracheal branches. Thus, glia-derived miR-274 coordinates growth of synaptic boutons and tracheal branches to modulate larval hypoxia responses.

Download Full-text

The Biology of Sialic Acids: Insights into their Structure, Metabolism and Function in Particular during Viral Infection

Glycosciences ◽

10.1002/9783527614738.ch13 ◽

2008 ◽

pp. 245-259 ◽

Cited By ~ 1

Author(s):

Werner Reutter ◽

Roger Stsche ◽

Peer Stehling ◽

Oliver Baum

Keyword(s):

Viral Infection ◽

Sialic Acids ◽

And Function

Download Full-text

Altered expression and in vivo lung function of protease-activated receptors during influenza A virus infection in mice

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00286.2003 ◽

2004 ◽

Vol 286 (2) ◽

pp. L388-L398 ◽

Cited By ~ 36

Author(s):

Rommel S. Lan ◽

Geoffrey A. Stewart ◽

Roy G. Goldie ◽

Peter J. Henry

Keyword(s):

Lung Function ◽

Viral Infection ◽

Influenza A ◽

Airway Disease ◽

Protease Activated Receptors ◽

Altered Expression ◽

Agonist Peptide ◽

Tracheal Epithelial Cells ◽

And Function

Protease-activated receptors (PARs) are widely distributed in human airways, and recent evidence indicates a role for PARs in the pathophysiology of inflammatory airway disease. To further investigate the role of PARs in airway disease, we determined the expression and function of PARs in a murine model of respiratory tract viral infection. PAR-1, PAR-2, PAR-3, and PAR-4 mRNA and protein were expressed in murine airways, and confocal microscopy revealed colocalization of PAR-2 and cyclooxygenase (COX)-2 immunostaining in basal tracheal epithelial cells. Elevated levels of PAR immunostaining, which was particularly striking for PAR-1 and PAR-2, were observed in the airways of influenza A/PR-8/34 virus-infected mice compared with sham-infected mice. Furthermore, increased PAR-1 and PAR-2 expression was associated with significant changes in in vivo lung function responses. PAR-1 agonist peptide potentiated methacholine-induced increases in airway resistance in anesthetized sham-infected mice (and in indomethacin-treated, virus-infected mice), but no such potentiation was observed in virus-infected mice. PAR-2 agonist peptide transiently inhibited methacholine-induced bronchoconstriction in sham-infected mice, and this effect was prolonged in virus-infected mice. These findings suggest that during viral infection, the upregulation of PARs in the airways is coupled to increased activation of COX and enhanced generation of bronchodilatory prostanoids.

Download Full-text

Intratracheal Poly(I:C) Exposure Accelerates the Immunological Disorder of Salivary Glands in Sjogren's-Like NOD/ShiLtJ Mice

Frontiers in Medicine ◽

10.3389/fmed.2021.645816 ◽

2021 ◽

Vol 8 ◽

Author(s):

Peng Hu ◽

Bingxia Ming ◽

Xuefen Wu ◽

Shaozhe Cai ◽

Jungen Tang ◽

...

Keyword(s):

Viral Infection ◽

Nod Mice ◽

Inflammatory Cells ◽

Poly I:C ◽

Intratracheal Administration ◽

Saliva Secretion ◽

Elevated Expression ◽

Immunological Disorder ◽

And Function ◽

Saliva Flow

Evidences have suggested that Sjogren's syndrome (SS) is associated with viral infection. The aim of this study was to investigate the involvement of respiratory viral poly(I:C) in the pathogenesis of SS and potential mechanisms using a SS-like NOD/ShiLtJ (NOD) mouse model. 5-week female NOD mice were intratracheally administered poly(I:C) every other day for 5 times to mimic viral infection. Pilocarpine induced saliva secretion was determined every 8 days. Submandibular glands (SMG) and lungs were harvested for the detection of pathological changes. We found that intratracheal administration of poly(I:C) significantly advanced and enhanced the reduction of saliva flow rate in NOD mice. Furthermore, poly(I:C) treatment aggravated the histopathological lesions and inflammatory cells infiltration in SMG. Accompanied by elevated expression of IFN cytokines and IL-33, Th1 activation was enhanced in SMG of poly(I:C)-treated NOD mice, but Th17 cells activation was unchanged among the groups. In addition, intratracheal poly(I:C) exposure promoted the expression of IL-33 and increased T cells proportion in the lung, which were consistent with the change in SMG. Therefore, intratracheal poly(I:C) exposure aggravated the immunological and function disorder of SMG in NOD mice.

Download Full-text

Effects of Length and Location on the Cellular Response to Double-Stranded RNA

Microbiology and Molecular Biology Reviews ◽

10.1128/mmbr.68.3.432-452.2004 ◽

2004 ◽

Vol 68 (3) ◽

pp. 432-452 ◽

Cited By ~ 79

Author(s):

Qiaoqiao Wang ◽

Gordon G. Carmichael

Keyword(s):

Cell Growth ◽

Viral Infection ◽

Normal Cell ◽

Cellular Response ◽

Viral Infections ◽

Cellular Responses ◽

Double Stranded Rna ◽

Antiviral Responses ◽

And Function ◽

In Cells

SUMMARY Since double-stranded RNA (dsRNA) has not until recently generally been thought to be deliberately expressed in cells, it has commonly been assumed that the major source of cellular dsRNA is viral infections. In this view, the cellular responses to dsRNA would be natural and perhaps ancient antiviral responses. While the cell may certainly react to some dsRNAs as an antiviral response, this does not represent the only response or even, perhaps, the major one. A number of recent observations have pointed to the possibility that dsRNA molecules are not seen only as evidence of viral infection or recognized for degradation because they cannot be translated. In some instances they may also play important roles in normal cell growth and function. The purpose of this review is to outline our current understanding of the fate of dsRNA in cells, with a focus on the apparent fact that their fates and functions appear to depend critically not only on where in the cell dsRNA molecules are found, but also on how long they are and perhaps on how abundant they are.

Download Full-text

ON EXPLORING EFFECTS OF MOLECULAR NOISE IN A SIMPLE VIRAL INFECTION MODEL

International Journal of Biomathematics ◽

10.1142/s1793524510000891 ◽

2010 ◽

Vol 03 (01) ◽

pp. 1-19 ◽

Cited By ~ 1

Author(s):

ZHI XIE ◽

DON KULASIRI

Keyword(s):

Viral Infection ◽

Regulatory Networks ◽

Virus Assembly ◽

Intrinsic Noise ◽

Genetic Regulatory Networks ◽

Infection Model ◽

Extrinsic Noise ◽

Living Organisms ◽

High Level ◽

And Function

Intrinsic and extrinsic noises are all believed to be important in the development and function of many living organisms. In this study, we investigate the sources of the intrinsic noise and the influence of the extrinsic noise on an intracellular viral infection system. The contribution of the intrinsic noise from each reaction is measured by means of a special form of stochastic differential equations (SDEs), chemical Langevin equation. The intrinsic noise of the system is a linear sum of the noise in each of the reactions. The intrinsic noise mainly arises from the degradation of mRNA and the transcription processes. We then study the effects of extrinsic noise by the means of a general form of SDE. It is found that the noise of the viral components grows logarithmically with the increasing noise intensities. The system is most susceptible to the noise in the virus assembly process. A high level of noise in this process can even inhibit the growth of the viruses. This study also demonstrates the utility of SDEs in analyzing genetic regulatory networks perturbed by either inherent or parametric stochasticity.

Download Full-text