Translation of Mycobacterium Survival Strategy to Develop a Lipo‐peptide based Fusion Inhibitor

2020 ◽  
Author(s):  
Pradip Kumar Tarafdar ◽  
Avijit Sardar ◽  
Aritraa Lahiri ◽  
Mithila Kamble ◽  
Amirul I. Mallick
Keyword(s):  
Fusion Inhibitor ◽  
Survival Strategy

scholarly journals Translation of Mycobacterium Survival Strategy to Develop a Lipo‐peptide based Fusion Inhibitor

2020 ◽  
Author(s):  
Pradip Kumar Tarafdar ◽  
Avijit Sardar ◽  
Aritraa Lahiri ◽  
Mithila Kamble ◽  
Amirul I. Mallick
Keyword(s):  
Fusion Inhibitor ◽  
Survival Strategy

scholarly journals Malaria parasites both repress host CXCL10 and use it as a cue for growth acceleration

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yifat Ofir-Birin ◽  
Hila Ben Ami Pilo ◽  
Abel Cruz Camacho ◽  
Ariel Rudik ◽  
Anna Rivkin ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Life Cycle ◽  
Cerebral Malaria ◽  
Survival Strategy ◽  
Parasitic Disease ◽  
Malaria Parasites ◽  
Sensing System ◽  
Rich Domain ◽  
Cargo Delivery ◽  
Low Levels

AbstractPathogens are thought to use host molecular cues to control when to initiate life-cycle transitions, but these signals are mostly unknown, particularly for the parasitic disease malaria caused by Plasmodium falciparum. The chemokine CXCL10 is present at high levels in fatal cases of cerebral malaria patients, but is reduced in patients who survive and do not have complications. Here we show a Pf ‘decision-sensing-system’ controlled by CXCL10 concentration. High CXCL10 expression prompts P. falciparum to initiate a survival strategy via growth acceleration. Remarkably, P. falciparum inhibits CXCL10 synthesis in monocytes by disrupting the association of host ribosomes with CXCL10 transcripts. The underlying inhibition cascade involves RNA cargo delivery into monocytes that triggers RIG-I, which leads to HUR1 binding to an AU-rich domain of the CXCL10 3’UTR. These data indicate that when the parasite can no longer keep CXCL10 at low levels, it can exploit the chemokine as a cue to shift tactics and escape.

scholarly journals Prefusion structure of human cytomegalovirus glycoprotein B and structural basis for membrane fusion

2021 ◽  
Vol 7 (10) ◽  
pp. eabf3178
Author(s):  
Yuhang Liu ◽  
Kyle P. Heim ◽  
Ye Che ◽  
Xiaoyuan Chi ◽  
Xiayang Qiu ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Human Cytomegalovirus ◽  
Transmembrane Domain ◽  
Proximal Region ◽  
Viral Envelope ◽  
Vaccine Antigen ◽  
Glycoprotein B ◽  
Structural Basis ◽  
Fusion Inhibitor ◽  
Host Cell Membrane

Human cytomegalovirus (HCMV) causes congenital disease with long-term morbidity. HCMV glycoprotein B (gB) transitions irreversibly from a metastable prefusion to a stable postfusion conformation to fuse the viral envelope with a host cell membrane during entry. We stabilized prefusion gB on the virion with a fusion inhibitor and a chemical cross-linker, extracted and purified it, and then determined its structure to 3.6-Å resolution by electron cryomicroscopy. Our results revealed the structural rearrangements that mediate membrane fusion and details of the interactions among the fusion loops, the membrane-proximal region, transmembrane domain, and bound fusion inhibitor that stabilized gB in the prefusion state. The structure rationalizes known gB antigenic sites. By analogy to successful vaccine antigen engineering approaches for other viral pathogens, the high-resolution prefusion gB structure provides a basis to develop stabilized prefusion gB HCMV vaccine antigens.

scholarly journals Structure-based discovery of Middle East respiratory syndrome coronavirus fusion inhibitor

2014 ◽  
Vol 5 (1) ◽  
Author(s):  
Lu Lu ◽  
Qi Liu ◽  
Yun Zhu ◽  
Kwok-Hung Chan ◽  
Lili Qin ◽  
...  
Keyword(s):  
Middle East ◽  
Middle East Respiratory Syndrome ◽  
Fusion Inhibitor

scholarly journals HIV-1 tropism for the central nervous system: Brain-derived envelope glycoproteins with lower CD4 dependence and reduced sensitivity to a fusion inhibitor

Virology ◽  
2006 ◽  
Vol 346 (1) ◽  
pp. 169-179 ◽  
Author(s):  
Julio Martín-García ◽  
Wei Cao ◽  
Angel Varela-Rohena ◽  
Matthew L. Plassmeyer ◽  
Francisco González-Scarano
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Envelope Glycoproteins ◽  
Fusion Inhibitor ◽  
The Central Nervous System ◽  
Hiv 1
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