Journal of Medical Virology, 2013, 01, 709─715

Impact of Escape Mutations on the Detection of Influenza Using the Rapid Influenza Diagnostic Test

Yi Hwajung, Kim Young-Hoon, Kim Jun-Sub, Lee Nam-Joo, Shin Kyeoungcheol, Choi Jang Hoon, Kwon Donghyok, Lee Joo-Yeon and Chun Kang

Abstract

During the 2009-10 pandemic, rapid influenza diagnostic tests (RIDTs) were used for viral detection due to their rapidity and ease of use. However, retrospective studies showed that RIDTs were poor at diagnosing pandemic viral infection. Currently, it is not possible to determine whether and how sequence changes of amino acids in pandemic or epidemic influenza viral antigens impact on clinical values of RIDTs, because the RIDTs have been not mapped. We investigated and defined whether and how the sensitivity and specificity of an RIDT (SD influenza Ag A/B/pdmH1N1) could be affected by escape-variations or mutations of influenza viral antigen through characterising the immunological properties of the antibodies used in the RIDT. Escape-mutants were generated by the cultivation of A/Korea/01/2009 with excess of the antibodies used in the RIDT. Escape-mutants not recognised by the RIDT were selected. Epitopes recognised by the RIDT were mapped by sequencing and immunological analysis of the escape-mutants, compared with wild isolates. The RIDT antibodies recognised epitopes on the Sa antigenic site and F subdomain in haemagglutinin. Variants bearing mutations on these epitopes were not detected by the RIDT.
The frequency of the escape-variants since the pandemic was calculated as 1.27% through in silico surveillance of the influenza sequence databases. Our investigation suggests that mapping RIDTs and making the information accessible to clinics will be helpful for determining whether RIDTs match to newly emergent strains and subtypes, prior to retrospective re-evaluation of the RIDTs with clinical specimens.

• ISBN or ISSN: 1096-9071

• 본 연구는 질병관리본부 연구개발과제(과제번호 2011-N43003-00) 연구비를 지원받아 수행되었습니다.
• This research was supported by a fund(code 2011-N43003-00) by Research of Korea Centers for Disease Control and Prevention.