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Liu, E.

Publications and source records attributed to Liu, E..

41 records · Page 3Linked to original sources
bioRxiv2019

Reticulon and CLIMP-63 control nanodomain organization of peripheral ER tubules

The endoplasmic reticulum (ER) is an expansive, membrane-enclosed organelle composed of smooth peripheral tubules and rough, ribosome-studded central ER sheets whose morphology is determined, in part, by the ER-shaping proteins, reticulon and CLIMP-63, respectively. Here, STimulated Emission Depletion (STED) super-resolution microscopy shows that reticulon and CLIMP-63 also control the organization and dynamics of peripheral ER tubule nanodomains. STED imaging shows that lumenal ERmoxGFP, membrane Sec61{beta}GFP, knock-in calreticulin-GFP and antibody-labeled ER resident proteins calnexin and derlin-1 are all localized to periodic puncta along the length of peripheral ER tubules that are not readily observable by diffraction limited confocal microscopy. Reticulon segregates away from and restricts lumenal blob length while CLIMP-63 associates with and increases lumenal blob length. Reticulon and CLIMP-63 also regulate the nanodomain distribution of ER resident proteins, being required for the preferential segregation of calnexin and derlin-1 puncta away from lumenal ERmoxGFP blobs. High-speed (40 ms/frame) live cell STED imaging shows that reticulon and CLIMP-63 control nanoscale compartmentalization of lumenal flow in peripheral ER tubules. Reticulon enhances and CLIMP-63 disrupts the local accumulation of lumenal ERmoxGFP at spatially defined sites along ER tubules. The ER shaping proteins reticulon and CLIMP-63 therefore control lumenal ER nanodomain dynamics, heterogeneity and interaction with ER resident proteins in peripheral ER tubules.

cell biology↗
bioRxiv2019

Respiratory syncytial virus activates Rab5a to suppress IRF1-dependent IFN-{lambda} production, subverting the antiviral defense of airway epithelial cells

Human respiratory syncytial virus (RSV) is a negative-strand RNA virus that causes severe acute pediatric respiratory tract infections worldwide. The limited effective antiviral options and lack of an effective vaccine against RSV highlight the need for a novel anti-viral therapy. One alternative is to identify and target the host factors required for viral infection. All viruses, including RSV, utilize cellular trafficking machinery to fulfill their life cycle in the infected host cells. Rab proteins mediate specific steps in intracellular membrane trafficking through the recruitment and tethering of fusion factors, and docking with actin- or microtubule-based motor proteins. Using RNA interference to knock down Rab proteins, we document that the micropinocytosis-associated Rab5a is required for RSV infection. RSV infection itself induces activation of Rab5a, and inhibition of this activation reduces RSV infection, but the mechanism for this effect remains unknown. Interferon (IFN) signaling plays an important role in innate immunity, and recent studies have identified IFN-{lambda} (lambda), a type III IFN, as the most important IFN for antiviral immune in response to RSV infection of mucosal epithelium. However, how the RSV-induced Rab5a suppresses airway epithelial antiviral immunity has not been unraveled. Here, we show that activated Rab5a inhibits IRF1-induced IFN-{lambda} production and IFN-{lambda}-mediated signal transduction via JAK-STAT1, thereby increasing viral replication. Rab5a knockdown by siRNA resulted in stimulation of IRF1, IFN-{lambda} and JAK-STAT1 expression, and suppressed viral growth. Our results highlight new role for Rab5a in RSV infection, such that its depletion inhibits RSV infection by stimulating the endogenous respiratory epithelial antiviral immunity, which suggests that Rab5a is a potential target for novel therapeutics against RSV infection. Author summaryRSV is the leading cause of lower respiratory tract infection in under 5 years old children. Worldwide. We identified Rab5a as a host factor involved in RSV infection via RNA interference to knock down familiar Rab proteins in human lung epithelial A549 cells infected with RSV. Rab5a belongs to Rab GTPases subfamily, which contributes to intracellular trafficking to promote virus infection. Knockdown or inactive (GDP-bound) Rab5a results in low infection and replication through stimulating IRF1, IFN-{lambda} and JAK-STAT1 expression, and suppressed viral growth. Besides, we propose that the regulation of Rab5a expression during RSV infection might be a viral strategy to promote its infectivity.

immunology↗
bioRxiv2017

Liver physiological T1rho dynamics associated with age and gender

PurposeUsing a single breathhold black blood sequence, the current study aims to understand the physiological ranges of liver T1rho relaxation for women and men.\n\nMaterials and MethodsThis volunteer study was conducted with institutional ethics committee approval, and included 62 females (age mean: 38.9 years; range: 18-75 years) and 34 males (age mean: 44.7 years, range: 24-80 years). MRI was conducted with a 3.0 T scanner, with six spin-lock times of 0, 10, 20, 25, 35, 50msec and a single breathhold of 12 seconds. Six slices were acquired for each examination.\n\nResultsFemale liver T1rho value ranged between 35.07 to 51.97ms, showed an age-dependent decrease with younger women had a higher measurement. Male Liver T1rho values ranged between 34.94 to 43.39 ms, and there was no evidential age-dependence. For females, there was a trend that liver T1rho value could be 4%-5% lower during menstrual phase than nonmenstrual phase. For both females and males, no evidential association was seen between body mass index and liver T1rho.\n\nConclusionLiver T1rho physiological value for males have relatively narrow distribution, while physiological value for females have wider distribution, and decreases with age.\n\nKey points1. Liver T1rho shows an age-dependency in women, with young women showing higher measurement. This age-dependency of liver T1rho measurement is not evidential in men. Post-menopausal women have similar liver T1rho value as men.\n\n2. Women at menstrual phase may have slight lower liver T1rho measurement.\n\n3. No association was noted between body mass index and liver T1rho\n\n4. When blood signal suppression sequence is used, in a population of 62 healthy women and 34 healthy men, the highest measured liver T1rho was 52 msec for young women, 44.7 msec for post-menopausal women, and 43.4 msec for men.

biophysics↗
bioRxiv2017

Severe infections emerge from the microbiome by adaptive evolution

Bacteria responsible for the greatest global mortality colonize the human microbiome far more frequently than they cause severe infections. Whether mutation and selection within the microbiome accompany infection is unknown. We investigated de novo mutation in 1163 Staphylococcus aureus genomes from 105 infected patients with nose-colonization. We report that 72% of infections emerged from the microbiome, with infecting and nose-colonizing bacteria showing parallel adaptive differences. We found 2.8-to-3.6-fold enrichments of protein-altering variants in genes responding to rsp, which regulates surface antigens and toxicity; agr, which regulates quorum-sensing, toxicity and abscess formation; and host-derived antimicrobial peptides. Adaptive mutations in pathogenesis-associated genes were 3.1-fold enriched in infecting but not nose-colonizing bacteria. None of these signatures were observed in healthy carriers nor at the species-level, suggesting disease-associated, short-term, within-host selection pressures. Our results show that infection, like a cancer of the microbiome, emerges through spontaneous adaptive evolution, raising new possibilities for diagnosis and treatment.\n\nOne Sentence SummaryLife-threatening S. aureus infections emerge from nose microbiome bacteria in association with repeatable adaptive evolution.

genomics↗