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Low pH-induced conformational change of rubella virus envelope proteins
Abstract:
Fusion of rubella virus-infected cells was induced by their brief treatment at pH below 6.0. Exposure of rubella virus to pH 5 caused an irreversible conformational change of the viral envelope glycoproteins, E1 and E2. The change was manifested in the marked reduction in both infectivity and haemagglutinating activity of the virus, the increased resistance of E1 and decreased resistance of E2 polypeptides to proteolytic digestion with trypsin, and the acquisition of liposome-binding activity of the virus. The above changes are presumed to mimic the events occurring in the acidic environment within endosomes following endocytosis of the virus.
Insights
Low pH triggers rubella virus-infected cell fusion by altering viral glycoproteins. This conformational change reduces virus infectivity and haemagglutination, mimicking endosomal entry.
Area of Science:
- Virology
- Cell Biology
- Biochemistry
Background:
- Rubella virus causes significant human disease.
- Viral entry into host cells is a critical step in infection.
- Understanding virus-host interactions is key to developing antiviral strategies.
Purpose of the Study:
- To investigate the effect of acidic pH on rubella virus structure and function.
- To elucidate the mechanism of rubella virus-induced cell fusion.
- To determine if low pH-induced changes mimic natural viral entry processes.
Main Methods:
- Treatment of rubella virus-infected cells with low pH buffers.
- Exposure of purified rubella virus to acidic pH (pH 5).
- Analysis of viral infectivity, haemagglutinating activity, and glycoprotein conformational changes using proteolytic digestion and liposome-binding assays.
Main Results:
- Brief exposure to pH below 6.0 induced fusion of rubella virus-infected cells.
- Exposure to pH 5 caused irreversible conformational changes in E1 and E2 glycoproteins.
- These changes led to reduced viral infectivity and haemagglutination, altered protease resistance, and induced liposome-binding activity.
Conclusions:
- Acidic pH induces rubella virus fusion by altering viral envelope glycoproteins.
- The observed changes in viral structure and function at low pH are consistent with events during endocytosis.
- This study provides insights into the molecular mechanisms of rubella virus entry and cell fusion.