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Effects of a single mutation in Chikungunya virus non-structural protein on virus infection in Aedes albopictus and mammalian cell lines / Jolene Fu Yin Ling

Chikungunya virus (CHIKV) has caused large-scale epidemics of fever, rash and arthritis since 2004. This unprecedented re-emergence has been mainly associated with mutations in genes encoding structural envelope proteins, providing increased fitness in the secondary vector Aedes (Ae.) albopictus....

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Main Author: Jolene Fu, Yin Ling
Format: Thesis
Published: 2020
Subjects:
R Medicine (General)
Online Access:http://studentsrepo.um.edu.my/11497/4/jolene.pdf
http://studentsrepo.um.edu.my/11497/
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spelling my.um.stud.114972023-01-02T22:10:26Z Effects of a single mutation in Chikungunya virus non-structural protein on virus infection in Aedes albopictus and mammalian cell lines / Jolene Fu Yin Ling Jolene Fu, Yin Ling R Medicine (General) Chikungunya virus (CHIKV) has caused large-scale epidemics of fever, rash and arthritis since 2004. This unprecedented re-emergence has been mainly associated with mutations in genes encoding structural envelope proteins, providing increased fitness in the secondary vector Aedes (Ae.) albopictus. In the 2008-2013 CHIKV outbreaks across Southeast Asia, an R82S mutation in non-structural protein 4 (nsP4) emerged early in Malaysia or Singapore and quickly became predominant. To determine whether this nsP4-R82S mutation provides a selective advantage in host cells which may have contributed to the epidemic, the fitness of infectious clone-derived CHIKV with nsP4- 82R and nsP4-82S were compared in Ae. albopictus and mammalian cell lines. Viral infectivity, dissemination and transmission in Ae. albopictus were not affected by the mutation when the two variants were tested separately. In competition, the nsP4-82R variant showed an advantage over nsP4-82S in dissemination to the salivary glands, but only in late infection (10 days). In human rhabdomyosarcoma (RD) and embryonic kidney (HEK-293T) cell lines coinfected at a 1:1 ratio, wild-type nsP4-82R virus was rapidly outcompeted by nsP4-82S virus as early as one passage (3 days). However, this fitness advantage was not observed in Vero cells. In conclusion, the nsP4-R82S mutation provides a greater selective advantage in human cells than in Ae. albopictus, which may explain its apparent natural selection during CHIKV spread in Southeast Asia. This is an unusual example of a naturally occurring mutation in a non-structural protein which may have facilitated epidemic transmission of CHIKV. 2020 Thesis NonPeerReviewed application/pdf http://studentsrepo.um.edu.my/11497/4/jolene.pdf Jolene Fu, Yin Ling (2020) Effects of a single mutation in Chikungunya virus non-structural protein on virus infection in Aedes albopictus and mammalian cell lines / Jolene Fu Yin Ling. Masters thesis, Universiti Malaya. http://studentsrepo.um.edu.my/11497/
institution Universiti Malaya
building UM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaya
content_source UM Student Repository
url_provider http://studentsrepo.um.edu.my/
topic R Medicine (General)
spellingShingle R Medicine (General)
Jolene Fu, Yin Ling
Effects of a single mutation in Chikungunya virus non-structural protein on virus infection in Aedes albopictus and mammalian cell lines / Jolene Fu Yin Ling
description Chikungunya virus (CHIKV) has caused large-scale epidemics of fever, rash and arthritis since 2004. This unprecedented re-emergence has been mainly associated with mutations in genes encoding structural envelope proteins, providing increased fitness in the secondary vector Aedes (Ae.) albopictus. In the 2008-2013 CHIKV outbreaks across Southeast Asia, an R82S mutation in non-structural protein 4 (nsP4) emerged early in Malaysia or Singapore and quickly became predominant. To determine whether this nsP4-R82S mutation provides a selective advantage in host cells which may have contributed to the epidemic, the fitness of infectious clone-derived CHIKV with nsP4- 82R and nsP4-82S were compared in Ae. albopictus and mammalian cell lines. Viral infectivity, dissemination and transmission in Ae. albopictus were not affected by the mutation when the two variants were tested separately. In competition, the nsP4-82R variant showed an advantage over nsP4-82S in dissemination to the salivary glands, but only in late infection (10 days). In human rhabdomyosarcoma (RD) and embryonic kidney (HEK-293T) cell lines coinfected at a 1:1 ratio, wild-type nsP4-82R virus was rapidly outcompeted by nsP4-82S virus as early as one passage (3 days). However, this fitness advantage was not observed in Vero cells. In conclusion, the nsP4-R82S mutation provides a greater selective advantage in human cells than in Ae. albopictus, which may explain its apparent natural selection during CHIKV spread in Southeast Asia. This is an unusual example of a naturally occurring mutation in a non-structural protein which may have facilitated epidemic transmission of CHIKV.
format Thesis
author Jolene Fu, Yin Ling
author_facet Jolene Fu, Yin Ling
author_sort Jolene Fu, Yin Ling
title Effects of a single mutation in Chikungunya virus non-structural protein on virus infection in Aedes albopictus and mammalian cell lines / Jolene Fu Yin Ling
title_short Effects of a single mutation in Chikungunya virus non-structural protein on virus infection in Aedes albopictus and mammalian cell lines / Jolene Fu Yin Ling
title_full Effects of a single mutation in Chikungunya virus non-structural protein on virus infection in Aedes albopictus and mammalian cell lines / Jolene Fu Yin Ling
title_fullStr Effects of a single mutation in Chikungunya virus non-structural protein on virus infection in Aedes albopictus and mammalian cell lines / Jolene Fu Yin Ling
title_full_unstemmed Effects of a single mutation in Chikungunya virus non-structural protein on virus infection in Aedes albopictus and mammalian cell lines / Jolene Fu Yin Ling
title_sort effects of a single mutation in chikungunya virus non-structural protein on virus infection in aedes albopictus and mammalian cell lines / jolene fu yin ling
publishDate 2020
url http://studentsrepo.um.edu.my/11497/4/jolene.pdf
http://studentsrepo.um.edu.my/11497/
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score 13.211869

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