The infectivity of progeny adenovirus in the presence of neutralizing antibody

Author:

Hirai Takamasa12,Sato Anna32,Koizumi Naoya2,Kurioka Yoh2,Suzuki Yui2,Kano Junpei2,Yamakawa Makie2,Nomura Tetsuya2,Fujii Makiko4,Sakurai Fuminori5ORCID,Mizuguchi Hiroyuki675,Watanabe Yoshiteru8,Utoguchi Naoki2

Affiliation:

1. Division of Cell-Based Therapeutic Products, National Institute of Health Sciences, Kanagawa, Japan

2. Department of Pharmaceutics and Biopharmaceutics, Showa Pharmaceutical University, Tokyo, Japan

3. Cosmetic Science Laboratory, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women’s University, Hyougo, Japan

4. Laboratory of Physical Chemistry, School of Pharmacy, Nihon University, Chiba, Japan

5. Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan

6. Global Center for Advanced Medical Engineering and Informatics, Osaka University, Osaka, Japan

7. iPS Cell-Based Research Project on Hepatic Toxicity and Metabolism, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan

8. Department of Pharmacy, Tohoku Medical and Pharmaceutical University Hospital, Miyagi, Japan

Abstract

Human adenoviruses (Ads), common pathogens that cause upper respiratory and gastrointestinal infections, are blocked by neutralizing antibodies (nAbs). However, Ads are not fully eliminated even in hosts with nAbs. In this study, we assessed the infectivity of progeny Ad serotype 5 (Ad5) in the presence of nAb. The infectivity of Ad5 was evaluated according to the expression of the Ad genome and reporter gene. Infection by wild-type Ad5 and Ad5 vector continued to increase until 3 days after infection even in the presence of nAb. We established an assay for determining the infection levels of progeny Ad5 using a sorting system with magnetic beads and observed little difference in progeny Ad5 counts in the presence and absence of nAb 1 day after infection. Moreover, progeny Ad5 in the presence of nAb more effectively infected coxsackievirus and adenovirus receptor (CAR)-positive cells than CAR-negative cells. We investigated the function of fiber proteins, which are the binding partners of CAR, during secondary infection, observing that fibre proteins spread from infected cells to adjacent cells in a CAR-dependent manner. In conclusion, this study revealed that progeny Ad5 could infect cells even in the presence of nAb, differing from the common features of the Ad5 infection cycle. Our findings may be useful for developing new therapeutic agents against Ad infection.

Funder

a Grant-in-Aid for Young Scientists of Showa Pharmaceutical University

Scholarship Fund for Young Researchers of The Promotion and Mutual Aid Corporation for Private Schools of Japan.

Publisher

Microbiology Society

Subject

Virology

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