Functional Dissection of the Dominant Role of CD55 in Protecting Vesicular Stomatitis Virus against Complement-Mediated Neutralization
The human complement system is an important part of the innate immune system. Its effector pathways largely mediate virus neutralization. Vesicular stomatitis virus (VSV) activates the classical pathway of the complement, leading to virus neutralization by lysis. Two host-derived membrane-associated...
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MDPI AG
2021-02-01
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| author | Nisha Asok Kumar Sreenath Muraleedharan Suma Umerali Kunnakkadan Joydeep Nag Reshma Koolaparambil Mukesh Douglas S. Lyles John Bernet Johnson |
| author_facet | Nisha Asok Kumar Sreenath Muraleedharan Suma Umerali Kunnakkadan Joydeep Nag Reshma Koolaparambil Mukesh Douglas S. Lyles John Bernet Johnson |
| author_sort | Nisha Asok Kumar |
| collection | DOAJ |
| description | The human complement system is an important part of the innate immune system. Its effector pathways largely mediate virus neutralization. Vesicular stomatitis virus (VSV) activates the classical pathway of the complement, leading to virus neutralization by lysis. Two host-derived membrane-associated regulators of complement activation (RCA), CD55 and CD46, which are incorporated into the VSV envelope during egress, confer protection by delaying/resisting complement-mediated neutralization. We showed previously that CD55 is more effective than CD46 in the inhibition of neutralization. In this study, we identified that, at the protein level, VSV infection resulted in the down-regulation of CD46 but not CD55. The mRNA of both the RCAs was significantly down-regulated by VSV, but it was delayed in the case of CD55. The immunoblot analysis of the levels of RCAs in the progeny virion harvested at three specific time intervals, points to an equal ratio of its distribution relative to viral proteins. Besides reconfirming the dominant role of CD55 over CD46 in shielding VSV from complement, our results also highlight the importance of the subtle modulation in the expression pattern of RCAs in a system naturally expressing them. |
| first_indexed | 2024-03-09T00:29:54Z |
| format | Article |
| id | doaj.art-ccbc9812e81548e9b4d061dbd4072012 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T00:29:54Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
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| spelling | doaj.art-ccbc9812e81548e9b4d061dbd40720122023-12-11T18:39:45ZengMDPI AGViruses1999-49152021-02-0113337310.3390/v13030373Functional Dissection of the Dominant Role of CD55 in Protecting Vesicular Stomatitis Virus against Complement-Mediated NeutralizationNisha Asok Kumar0Sreenath Muraleedharan Suma1Umerali Kunnakkadan2Joydeep Nag3Reshma Koolaparambil Mukesh4Douglas S. Lyles5John Bernet Johnson6Pathogen Biology, Virology, Rajiv Gandhi Center for Biotechnology, Thiruvananthapuram, Kerala 695014, IndiaPathogen Biology, Virology, Rajiv Gandhi Center for Biotechnology, Thiruvananthapuram, Kerala 695014, IndiaPathogen Biology, Virology, Rajiv Gandhi Center for Biotechnology, Thiruvananthapuram, Kerala 695014, IndiaPathogen Biology, Virology, Rajiv Gandhi Center for Biotechnology, Thiruvananthapuram, Kerala 695014, IndiaPathogen Biology, Virology, Rajiv Gandhi Center for Biotechnology, Thiruvananthapuram, Kerala 695014, IndiaDepartment of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC 27101, USAPathogen Biology, Virology, Rajiv Gandhi Center for Biotechnology, Thiruvananthapuram, Kerala 695014, IndiaThe human complement system is an important part of the innate immune system. Its effector pathways largely mediate virus neutralization. Vesicular stomatitis virus (VSV) activates the classical pathway of the complement, leading to virus neutralization by lysis. Two host-derived membrane-associated regulators of complement activation (RCA), CD55 and CD46, which are incorporated into the VSV envelope during egress, confer protection by delaying/resisting complement-mediated neutralization. We showed previously that CD55 is more effective than CD46 in the inhibition of neutralization. In this study, we identified that, at the protein level, VSV infection resulted in the down-regulation of CD46 but not CD55. The mRNA of both the RCAs was significantly down-regulated by VSV, but it was delayed in the case of CD55. The immunoblot analysis of the levels of RCAs in the progeny virion harvested at three specific time intervals, points to an equal ratio of its distribution relative to viral proteins. Besides reconfirming the dominant role of CD55 over CD46 in shielding VSV from complement, our results also highlight the importance of the subtle modulation in the expression pattern of RCAs in a system naturally expressing them.https://www.mdpi.com/1999-4915/13/3/373vesicular stomatitis viruscomplementvirus neutralizationviral resistancemembrane cofactor protein (CD46)decay accelerating factor (CD55) |
| spellingShingle | Nisha Asok Kumar Sreenath Muraleedharan Suma Umerali Kunnakkadan Joydeep Nag Reshma Koolaparambil Mukesh Douglas S. Lyles John Bernet Johnson Functional Dissection of the Dominant Role of CD55 in Protecting Vesicular Stomatitis Virus against Complement-Mediated Neutralization Viruses vesicular stomatitis virus complement virus neutralization viral resistance membrane cofactor protein (CD46) decay accelerating factor (CD55) |
| title | Functional Dissection of the Dominant Role of CD55 in Protecting Vesicular Stomatitis Virus against Complement-Mediated Neutralization |
| title_full | Functional Dissection of the Dominant Role of CD55 in Protecting Vesicular Stomatitis Virus against Complement-Mediated Neutralization |
| title_fullStr | Functional Dissection of the Dominant Role of CD55 in Protecting Vesicular Stomatitis Virus against Complement-Mediated Neutralization |
| title_full_unstemmed | Functional Dissection of the Dominant Role of CD55 in Protecting Vesicular Stomatitis Virus against Complement-Mediated Neutralization |
| title_short | Functional Dissection of the Dominant Role of CD55 in Protecting Vesicular Stomatitis Virus against Complement-Mediated Neutralization |
| title_sort | functional dissection of the dominant role of cd55 in protecting vesicular stomatitis virus against complement mediated neutralization |
| topic | vesicular stomatitis virus complement virus neutralization viral resistance membrane cofactor protein (CD46) decay accelerating factor (CD55) |
| url | https://www.mdpi.com/1999-4915/13/3/373 |
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