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  • 1
    In: Diseases, MDPI AG, Vol. 6, No. 3 ( 2018-07-13), p. 64-
    Abstract: Lassa fever virus (LFV) belongs to the Arenaviridae family and can cause acute hemorrhagic fever in humans. The LFV Z protein plays a central role in virion assembly and egress, such that independent expression of LFV Z leads to the production of virus-like particles (VLPs) that mimic egress of infectious virus. LFV Z contains both PTAP and PPPY L-domain motifs that are known to recruit host proteins that are important for mediating efficient virus egress and spread. The viral PPPY motif is known to interact with specific host WW-domain bearing proteins. Here we identified host WW-domain bearing protein BCL2 Associated Athanogene 3 (BAG3) as a LFV Z PPPY interactor using our proline-rich reading array of WW-domain containing mammalian proteins. BAG3 is a stress-induced molecular co-chaperone that functions to regulate cellular protein homeostasis and cell survival via Chaperone-Assisted Selective Autophagy (CASA). Similar to our previously published findings for the VP40 proteins of Ebola and Marburg viruses, our results using VLP budding assays, BAG3 knockout cells, and confocal microscopy indicate that BAG3 is a WW-domain interactor that negatively regulates egress of LFV Z VLPs, rather than promoting VLP release. Our results suggest that CASA and specifically BAG3 may represent a novel host defense mechanism, whereby BAG3 may dampen egress of several hemorrhagic fever viruses by interacting and interfering with the budding function of viral PPxY-containing matrix proteins.
    Type of Medium: Online Resource
    ISSN: 2079-9721
    Language: English
    Publisher: MDPI AG
    Publication Date: 2018
    detail.hit.zdb_id: 2720869-2
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  • 2
    In: Animals, MDPI AG, Vol. 12, No. 5 ( 2022-02-25), p. 588-
    Abstract: This study investigated the impacts of metabolizable protein (MP) restriction in primiparous heifers during mid- and/or late-gestation on progeny performance and carcass characteristics. Heifers were allocated to 12 pens in a randomized complete block design. The factorial treatment structure included two stages of gestation (mid- and late-) and two levels of dietary protein (control (CON); ~101% of MP requirements and restricted (RES); ~80% of MP requirements). Half of the pens on each treatment were randomly reassigned to the other treatment at the end of mid-gestation. Progeny were finished in a GrowSafe feeding system and carcass measurements were collected. Gestation treatment x time interactions indicated that MP restriction negatively influenced heifer body weight (BW), body condition score, and longissimus muscle (LM) area (p 〈 0.05), but not fat thickness (p 〉 0.05). Treatment did not affect the feeding period, initial or final BW, dry matter intake, or average daily gain of progeny (p 〉 0.05). The progeny of dams on the RES treatment in late gestation had a greater LM area (p = 0.04), but not when adjusted on a hot carcass weight basis (p 〉 0.10). Minimal differences in the animal performance and carcass characteristics suggest that the level of MP restriction imposed during mid- and late-gestation in this study did not have a significant developmental programming effect.
    Type of Medium: Online Resource
    ISSN: 2076-2615
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2606558-7
    SSG: 23
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  • 3
    In: Viruses, MDPI AG, Vol. 13, No. 2 ( 2021-02-12), p. 288-
    Abstract: Filoviruses Ebola (EBOV) and Marburg (MARV) are devastating high-priority pathogens capable of causing explosive outbreaks with high human mortality rates. The matrix proteins of EBOV and MARV, as well as eVP40 and mVP40, respectively, are the key viral proteins that drive virus assembly and egress and can bud independently from cells in the form of virus-like particles (VLPs). The matrix proteins utilize proline-rich Late (L) domain motifs (e.g., PPxY) to hijack specific host proteins that contain WW domains, such as the HECT family E3 ligases, to facilitate the last step of virus–cell separation. We identified E3 ubiquitin ligase Smad Ubiquitin Regulatory Factor 2 (SMURF2) as a novel interactor with VP40 that positively regulates VP40 VLP release. Our results show that eVP40 and mVP40 interact with the three WW domains of SMURF2 via their PPxY motifs. We provide evidence that the eVP40–SMURF2 interaction is functional as the expression of SMURF2 positively regulates VLP egress, while siRNA knockdown of endogenous SMURF2 decreases VLP budding compared to controls. In sum, our identification of novel interactor SMURF2 adds to the growing list of identified host proteins that can regulate PPxY-mediated egress of VP40 VLPs. A more comprehensive understanding of the modular interplay between filovirus VP40 and host proteins may lead to the development of new therapies to combat these deadly infections.
    Type of Medium: Online Resource
    ISSN: 1999-4915
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2516098-9
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  • 4
    In: Nutrients, MDPI AG, Vol. 12, No. 4 ( 2020-04-19), p. 1144-
    Abstract: Aerobic exercise and thermal stress instigate robust challenges to the immune system. Various attempts to modify or supplement the diet have been proposed to bolster the immune system responses. The purpose of this study was to identify the impact of yeast beta-glucan (Saccharomyces cerevisiae) supplementation on exercise-induced muscle damage and inflammation. Healthy, active men (29.6 ± 6.7 years, 178.1 ± 7.2 cm, 83.2 ± 11.2 kg, 49.6 ± 5.1 mL/kg/min, n = 16) and women (30.1 ± 8.9 years, 165.6 ± 4.1 cm, 66.7 ± 10.0 kg, 38.7 ± 5.8 mL/kg/min, n = 15) were randomly assigned in a double-blind and cross-over fashion to supplement for 13 days with either 250 mg/day of yeast beta-glucan (YBG) or a maltodextrin placebo (PLA). Participants arrived fasted and completed a bout of treadmill exercise at 55% peak aerobic capacity (VO2Peak) in a hot (37.2 ± 1.8 °C) and humid (45.2 ± 8.8%) environment. Prior to and 0, 2, and 72 h after completing exercise, changes in white blood cell counts, pro- and anti-inflammatory cytokines, markers of muscle damage, markers of muscle function, soreness, and profile of mood states (POMS) were assessed. In response to exercise and heat, both groups experienced significant increases in white blood cell counts, plasma creatine kinase and myoglobin, and soreness along with reductions in peak torque and total work with no between-group differences. Concentrations of serum pro-inflammatory cytokines in YBG were lower than PLA for macrophage inflammatory protein 1β (MIP-1β) (p = 0.044) and tended to be lower for interleukin 8 (IL-8) (p = 0.079), monocyte chemoattractment protein 1 (MCP-1) (p = 0.095), and tumor necrosis factor α (TNF-α) (p = 0.085). Paired samples t-tests using delta values between baseline and 72 h post-exercise revealed significant differences between groups for IL-8 (p = 0.044, 95% Confidence Interval (CI): (0.013, 0.938, d = −0.34), MCP-1 (p = 0.038, 95% CI: 0.087, 2.942, d = −0.33), and MIP-1β (p = 0.010, 95% CI: 0.13, 0.85, d = −0.33). POMS outcomes changed across time with anger scores in PLA exhibiting a sharper decline than YBG (p = 0.04). Vigor scores (p = 0.04) in YBG remained stable while scores in PLA were significantly reduced 72 h after exercise. In conclusion, a 13-day prophylactic period of supplementation with 250 mg of yeast-derived beta-glucans invoked favorable changes in cytokine markers of inflammation after completing a prolonged bout of heated treadmill exercise.
    Type of Medium: Online Resource
    ISSN: 2072-6643
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2518386-2
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