Dengue virus (DENV) causes dengue fever and severe hemorrhagic fever in humans and is primarily transmitted by Aedes aegypti and A. albopictus mosquitoes. The incidence of DENV infection has been ...gradually increasing in recent years due to global urbanization and international travel. Understanding the virulence determinants in host and vector transmissibility of emerging epidemic DENV will be critical to combat potential outbreaks. The DENV serotype 2 (DENV-2), which caused a widespread outbreak in Taiwan in 2015 (TW2015), is of the Cosmopolitan genotype and is phylogenetically related to the virus strain linked to another large outbreak in Indonesia in 2015. We found that the TW2015 virus was highly virulent in type I and type II interferon-deficient mice, with robust replication in spleen, lung, and intestine. The TW2015 virus also had high transmissibility to Aedes mosquitoes and could be effectively spread in a continuous mosquitoes-mouse-mosquitoes-mouse transmission cycle. By making 16681-based mutants carrying different segments of the TW2015 virus, we identified the structural pre-membrane (prM) and envelope (E) genes as key virulence determinants in the host, with involvement in the high transmissibility of the TW2015 virus in mosquitoes. The transmission mouse model will make a useful platform for evaluation of DENV with high epidemic potential and development of new strategies against dengue outbreaks.
An effective COVID-19 vaccine against broad SARS-CoV-2 variants is still an unmet need. In the study, the vesicular stomatitis virus (VSV)-based vector was used to express the SARS-CoV-2 Spike ...protein to identify better vaccine designs. The replication-competent of the recombinant VSV-spike virus with C-terminal 19 amino acid truncation (SΔ19 Rep) was generated. A single dose of SΔ19 Rep intranasal vaccination is sufficient to induce protective immunity against SARS-CoV-2 infection in hamsters. All the clones isolated from the SΔ19 Rep virus contained R682G mutation located at the Furin cleavage site. An additional S813Y mutation close to the TMPRSS2 cleavage site was identified in some clones. The enzymatic processing of S protein was blocked by these mutations. The vaccination of the R682G-S813Y virus produced a high antibody response against S protein and a robust S protein-specific CD8
T cell response. The vaccinated animals were protected from the lethal SARS-CoV-2 (delta variant) challenge. The S antigen with resistance to enzymatic processes by Furin and TMPRSS2 will provide better immunogenicity for vaccine design.
Zika virus (ZIKV) is primarily transmitted by Aedes mosquitoes in the subgenus Stegomyia but can also be transmitted sexually and vertically in humans. STAT1 is an important downstream factor that ...mediates type I and II interferon signaling. In the current study, we showed that mice with STAT1 knockout (Stat1-/-) were highly susceptible to ZIKV infection. As low as 5 plaque-forming units of ZIKV could cause viremia and death in Stat1-/- mice. ZIKV replication was initially detected in the spleen but subsequently spread to the brain with concomitant reduction of the virus in the spleen in the infected mice. Furthermore, ZIKV could be transmitted from mosquitoes to Stat1-/- mice back to mosquitoes and then to naïve Stat1-/- mice. The 50% mosquito infectious dose of viremic Stat1-/- mouse blood was close to 810 focus-forming units (ffu)/ml. Our further studies indicated that the activation of macrophages and conventional dendritic cells were likely critical for the resolution of ZIKV infection. The newly developed mouse and mosquito transmission models for ZIKV infection will be useful for the evaluation of antiviral drugs targeting the virus, vector, and host.
Post-translational modifications (PTMs), such as glycosylation and palmitoylation, are critical to protein folding, stability, intracellular trafficking, and function. Understanding regulation of ...PTMs of SARS-CoV-2 spike (S) protein could help the therapeutic drug design. Herein, the VSV vector was used to produce SARS-CoV-2 S pseudoviruses to examine the roles of the 611LYQD614 and cysteine-rich motifs in S protein maturation and virus infectivity. Our results show that 611LY612 mutation alters S protein intracellular trafficking and reduces cell surface expression level. It also changes S protein glycosylation pattern and decreases pseudovirus infectivity. The S protein contains four cysteine-rich clusters with clusters I and II as the main palmitoylation sites. Mutations of clusters I and II disrupt S protein trafficking from ER-to-Golgi, suppress pseudovirus production, and reduce spike-mediated membrane fusion activity. Taken together, glycosylation and palmitoylation orchestrate the S protein maturation processing and are critical for S protein-mediated membrane fusion and infection.
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•611LY612 mutation alters the glycosylation pattern of the SARS-CoV-2 S protein•611LY612 mutation reduces S protein surface expression level•Palmitoylation targets mature S protein to the Golgi and plasma membrane•Palmitoylation is required for pseudovirus and SARS-CoV-2 production
Biochemistry; Virology; Cell biology.
This paper proposes a two-stage planning algorithm for 3-leg free-climbing robots. The algorithm consists of global path planner and local motion planner. Firstly, the proposed algorithm distributes ...climbing points to Delaunay triangle mesh. The global planner plans a sequence of Delaunay triangles from the start configuration to goal configuration. Then, the latter plans the transition configurations between two adjacent triangles of the trajectory. The local motion algorithm uses the inverse Jacobian matrix to derive the positions and angles of joints for all configurations. Since the proposed algorithm directly uses spatial information of the workspace to plan a path, it is more efficient than configuration-space based approaches. Simulation results show that the proposed algorithm works well.
碩士
國立雲林科技大學
資訊工程系碩士班
100
In this thesis, a novel geometric based path planning algorithm is proposed for 3-leg free-climbing robots. The algorithm consists of global path planner and local motion ...planner. The global path planner plans a trajectory which is a sequence of Delaunay triangles composed of 3 climbing points. Then, the motion planner plans four basic transiting configurations along a predetermined trajectory between two adjacent triangles of the trajectory. The four basic configurations including the start configuration, the intermediate configuration, the intermediate-goal configuration and the final configuration can be obtained by Jacobian-based algorithm. Therefore, more configurations between two consecutive basic configurations can be obtained by linear interpolation.
Since the proposed algorithm directly uses spatial occupancy information of the workspace to plan a path, it is more efficient than configuration-space based approaches. Simulation results show that the proposed algorithm works w
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