Poxviruses are unusual DNA viruses that replicate in the cytoplasm. To do so, they encode approximately 100 immunomodulatory proteins that counteract cytosolic nucleic acid sensors such as cGAMP synthase (cGAS) along with several other antiviral response pathways. Yet most of these immunomodulators are expressed very early in infection while many are variable host range determinants, and significant gaps remain in our understanding of poxvirus sensing and evasion strategies.
View Article and Find Full Text PDFRecent studies have begun to reveal the complex and multifunctional roles of -methyladenosine (mA) modifications and their associated writer, reader, and eraser proteins in infection by diverse RNA and DNA viruses. However, little is known about their regulation and functions during infection by several viruses, including poxviruses. Here, we show that members of the YTH Domain Family (YTHDF), in particular YTHDF2, are downregulated as the prototypical poxvirus, vaccinia virus (VacV) enters later stages of replication in a variety of natural target cell types, but not in commonly used transformed cell lines wherein the control of YTHDF2 expression appears to be dysregulated.
View Article and Find Full Text PDFMethylation at the N6 position of adenosine (m6A) is a highly prevalent and reversible modification within eukaryotic mRNAs that has been linked to many stages of RNA processing and fate. Recent studies suggest that m6A deposition and proteins involved in the m6A pathway play a diverse set of roles in either restricting or modulating the lifecycles of select viruses. Here, we report that m6A levels are significantly increased in cells infected with the oncogenic human DNA virus Kaposi's sarcoma-associated herpesvirus (KSHV).
View Article and Find Full Text PDFPlasmacytoid dendritic cells (pDC) are type I interferon-producing cells with critical functions in a number of human illnesses; however, their molecular regulation is incompletely understood. Here we show the role of Src family kinases (SFK) in mouse and human pDCs. pDCs express Fyn and Lyn and their activating residues are phosphorylated both before and after Toll-like receptor (TLR) stimulation.
View Article and Find Full Text PDFType I IFNs (IFN-I) are key innate mediators that create a profound antiviral state and orchestrate the activation of almost all immune cells. Plasmacytoid dendritic cells (pDCs) are the most powerful IFN-I-producing cells and play important roles during viral infections, cancer, and autoimmune diseases. By comparing gene expression profiles of murine pDCs and conventional DCs, we found that CD28, a prototypic T cell stimulatory receptor, was highly expressed in pDCs.
View Article and Find Full Text PDFTranscription of herpesviral late genes is stimulated after the onset of viral DNA replication but otherwise restricted. Late gene expression in gammaherpesviruses requires the coordination of six early viral proteins, termed viral transactivation factors (vTFs). Here, we mapped the organization of this protein complex for Kaposi's sarcoma-associated herpesvirus.
View Article and Find Full Text PDFUnlabelled: Rapid innate responses to viral encounters are crucial to shaping the outcome of infection, from viral clearance to persistence. Transforming growth factor β (TGF-β) is a potent immune suppressor that is upregulated early upon viral infection and maintained during chronic infections in both mice and humans. However, the role of TGF-β signaling in regulating individual cell types in vivo is still unclear.
View Article and Find Full Text PDFJ Appl Physiol (1985)
October 1999
We sought to determine whether hydrostatic pressure contributed to bradycardia and hypoventilation in hyperbaria. Eight men were studied during exercise at 50, 150, and 250 W while breathing 1) air at 1 bar, 2) helium-oxygen (He-O(2)) at 5.5 bar, 3) sulfur hexafluoride-oxygen (SF(6)-O(2)) at 1.
View Article and Find Full Text PDFJ Appl Physiol (1985)
May 1990
The effects of increased airway resistance on lung volumes and pattern of breathing were studied in eight subjects performing leg exercise on a cycle ergometer. Airway resistance was changed 1) by increasing the density (D) of the respired gas by a factor of 4.2 and changing the inspired gas from O2 at 1.
View Article and Find Full Text PDFJ Appl Physiol (1985)
August 1987
The maximal contractile force (peak torque) of the quadriceps femoris was studied during 60 repeated unilateral dynamic knee extensions in nine subjects under three different conditions, viz., during air breathing at normal (1 ATA) and raised (6 ATA) ambient pressures and during O2 breathing at 1.3 ATA.
View Article and Find Full Text PDFActa Physiol Scand
September 1984
We studied changes in breathing pattern and mouth occlusion pressure (P0.1) in 11 healthy subjects performing graded steady-state exercise on a cycle ergometer up to the maximal load sustainable for 4 min. With increasing work intensity both the tidal volume (VT) and end-inspiratory volume relations to inspiratory (TI) and expiratory (TE) durations were linear in the moderate work load range; in the high load range VT and end-inspiratory volume tended to plateau with further decreases in TI and TE.
View Article and Find Full Text PDFActa Physiol Scand
April 1984
To analyze the interdependence of respiratory drive, ventilation and airway resistance during exercise, mouth occlusion pressure (P0.1), minute ventilation (V) and mean inspiratory flow (VT/TI) were studied in eight normal subjects performing cycle-ergometer exercise at loads ranging from 0 W to 200 W under two different ambient conditions: 1) during oxygen breathing at 1.3 ATA, and 2) during air breathing at 6 ATA (PO2 = 1.
View Article and Find Full Text PDFThe interrelationships of ventilation (V), tidal volume (VT), inspiratory (T1), expiratory (TE) and total breath (Ttot) durations, mean inspiratory (VT/TI) and expiratory (VT/TE) flows, and lung volumes were studied in normal subjects at rest and during exercise on a cycle ergometer. The ergometric load was increased by 10 W every minute, from zero W to 200 W. The TI/Ttot ratio increased with V in the range 15 to 60 1 X min-1, indicating that with increasing V the rate of increase of VT/TI decreased whereas that of VT/TE increased.
View Article and Find Full Text PDFRespir Physiol
March 1983
Mouth occlusion pressure (P0.1), minute ventilation (V), and mean inspiratory and expiratory flows were studied in eight normal subjects at rest and during exercise on a cycle ergometer, the load of which was increased in steps of 10 W every minute. All four variables rose curvilinearly as the load was increased from 0 to 200 W.
View Article and Find Full Text PDFJ Appl Physiol Respir Environ Exerc Physiol
April 1981
Pulmonary ventilation (V) and the interrelationships of airflow, transpulmonary pressure, and lung volume during inspiration and expiration were studied in eight healthy subjects who performed maximal exercise (MEx; 140% VO2 max), 15-s maximal voluntary ventilation (MVV), and forced inspiratory and expiratory vital capacity (FVC) maneuvers at 1, 3, and 6 ATA. Maximal exercise ventilation and MVV amounted to 149 +/- 7 (mean +/- SE) and 193 +/- 9 l . min-1, respectively, at 1 ATA and were both reduced by approximately 37% at 3 ATA and by 50% at 6 ATA.
View Article and Find Full Text PDFJ Appl Physiol Respir Environ Exerc Physiol
June 1980
We studied the respiratory and circulatory effects in six healthy supine volunteers of continuous negative-pressure breathing (CNPB) at -15 and -30 cmH2O at rest and during dynamic leg exercies at 50% of individual working capacity. CNPB had no significant effects on respiratory minute volume, tidal volume, or arterial carbon dioxide tension. Mean arterial pressure remained essentially unchanged both at rest and during exercise, signifying that the reductions in intrathoracic pressure caused corresponding increases in left ventricular afterload.
View Article and Find Full Text PDFUndersea Biomed Res
March 1979
Eight amateur divers took part in crossover experiments to study the combined effects of ethanol (0.72 g/kg b.wt.
View Article and Find Full Text PDFActa Physiol Scand
February 1979
To investigate the effects of sustained positive-pressure breathing (PPB) on the adaptation of respiratory and circulatory functions to exercise, 8 healthy volunteers were exposed to PPB of air at 15 and 30 cm H2O in the supine position at rest and while performing leg exercise at 50% of individual maximal working capacity. PPB was both subjectively and objectively better tolerated when combined with exercise than it was at rest. PPB at 30 cm H2O resulted in marked hyperventilation with alkalosis in the resting condition, but did not significantly affect respiratory minute volume, blood gases or acid-base balance during exercise.
View Article and Find Full Text PDFUndersea Biomed Res
December 1978
In an attempt to determine the roles of nitrogen, oxygen, and carbon dioxide in compressed-air narcosis, the effects on performance (mental function and manual dexterity) of adding CO2 in various concentrations to the inspired gas under three different conditions were studied in eight healthy male volunteers. The three conditions were: (1) air breathing at 1.3 ATA; (2) oxygen breathing at 1.
View Article and Find Full Text PDFJ Appl Physiol Respir Environ Exerc Physiol
November 1978
The effects of hyberbaric nitrogen on the responses of ventilation and central inspiratory activity (CIA) to progressive hypercapnia were studied in eight subjects rebreathing a) O2 at an ambient pressure of 1.3 bar (control), and b) air at 6.1 bar (PO2 = 1.
View Article and Find Full Text PDFCardiorespiratory and metabolic responses to steady-state dynamic leg exercise were studied in seven male subjects who performed positive and negative work on a modified Krogh cycle ergometer at loads of 0, 16, 33, 49, 98, and 147 W with a pedalling rate of 60 rpm. In positive work, O2 uptake increased with the ergometric load in a parabolic fashion. Net O2 uptake averaged averaged 220 ml-min-1 at 0 W (loadless pedalling), and was 75 ml-min-1 lower at the point of physiological minimum load which occurred in negative work at approximately 9 W.
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