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Rubella Virus: First Calcium-Requiring Viral Fusion Protein


Rubella virus (RuV) is a small enveloped RNA virus causing mild disease in children. However, infection of pregnant women can produce fetal death or congenital rubella syndrome, a constellation of severe birth defects including cataracts, hearing loss, heart disease and developmental delays. While vaccination has greatly reduced disease in the developed world, rubella remains prevalent in developing countries and other undervaccinated populations. RuV infects cells by endocytic uptake and a low pH-triggered membrane fusion reaction mediated by the viral E1 protein. The postfusion structure of E1 revealed a metal ion complexed at the membrane-interacting tip of the protein. Here we demonstrated that RuV infection and fusion are completely dependent on calcium, which could not be replaced functionally by any other metal that was tested. In the absence of calcium, RuV entry and low pH-conformational changes were unchanged, but E1's interaction with the target membrane was specifically blocked. Mutations of the calcium-binding residues in E1 caused a similar inhibition of E1 membrane interaction, fusion and infection. Thus, RuV E1 is the first known example of a calcium-dependent virus fusion protein.


Vyšlo v časopise: Rubella Virus: First Calcium-Requiring Viral Fusion Protein. PLoS Pathog 10(12): e32767. doi:10.1371/journal.ppat.1004530
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004530

Souhrn

Rubella virus (RuV) is a small enveloped RNA virus causing mild disease in children. However, infection of pregnant women can produce fetal death or congenital rubella syndrome, a constellation of severe birth defects including cataracts, hearing loss, heart disease and developmental delays. While vaccination has greatly reduced disease in the developed world, rubella remains prevalent in developing countries and other undervaccinated populations. RuV infects cells by endocytic uptake and a low pH-triggered membrane fusion reaction mediated by the viral E1 protein. The postfusion structure of E1 revealed a metal ion complexed at the membrane-interacting tip of the protein. Here we demonstrated that RuV infection and fusion are completely dependent on calcium, which could not be replaced functionally by any other metal that was tested. In the absence of calcium, RuV entry and low pH-conformational changes were unchanged, but E1's interaction with the target membrane was specifically blocked. Mutations of the calcium-binding residues in E1 caused a similar inhibition of E1 membrane interaction, fusion and infection. Thus, RuV E1 is the first known example of a calcium-dependent virus fusion protein.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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