Oseltamivir inhibits influenza virus replication and transmission following ocular-only aerosol inoculation of ferrets

被引:16
作者
Belser, Jessica A. [1 ]
Maines, Taronna R. [1 ]
Creager, Hannah M. [1 ,2 ]
Katz, Jacqueline M. [1 ]
Tumpey, Terrence M. [1 ]
机构
[1] Ctr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA
[2] Emory Univ, Microbiol & Mol Genet Grad Program, Atlanta, GA 30322 USA
关键词
Influenza virus; Oseltamivir (Tamiflu); Ferret model; Antiviral; Aerosol; Transmission; A VIRUS; INFECTION; H5N1; TROPISM; PATHOGENESIS; VIRULENCE; REGIMENS; EFFICACY; THERAPY; MODEL;
D O I
10.1016/j.virol.2015.06.020
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Ocular exposure to influenza virus represents an alternate route of virus entry capable of establishing a respiratory infection in mammals, but the effectiveness of currently available antiviral treatments to limit virus replication within ocular tissue or inhibit virus spread from ocular sites to the respiratory tract is poorly understood. Using an inoculation method that delivers an aerosol inoculum exclusively to the ocular surface, we demonstrate that oral oseltamivir administration following ocular-only aerosol inoculation with multiple avian and human influenza viruses protected ferrets from a fatal and systemic infection, reduced clinical signs and symptoms of illness, and decreased virus transmissibility to susceptible contacts when a respiratory infection was initiated. The presence of oseltamivir further inhibited influenza virus replication in primary human corneal epithelial cells. These findings provide critical experimental evidence supporting the use of neuraminidase inhibitors during outbreaks of influenza virus resulting in ocular disease or following ocular exposure. Published by Elsevier Inc.
引用
收藏
页码:305 / 312
页数:8
相关论文
共 41 条
[1]   Zoonotic potential of highly pathogenic avian H7N3 influenza viruses from Pakistan [J].
Aamir, Uzma B. ;
Naeem, Khalid ;
Ahmed, Zaheer ;
Obert, Caroline A. ;
Franks, John ;
Krauss, Scott ;
Seiler, Patrick ;
Webster, Robert G. .
VIROLOGY, 2009, 390 (02) :212-220
[2]  
Abdel-Ghafar AN, 2008, NEW ENGL J MED, V358, P261, DOI 10.1056/NEJMra0707279
[3]  
Avian influenza, 2007, EUROSURVEILLANCE, V12
[4]   Influenza Virus Infectivity and Virulence following Ocular-Only Aerosol Inoculation of Ferrets [J].
Belser, Jessica A. ;
Gustin, Kortney M. ;
Katz, Jacqueline M. ;
Maines, Taronna R. ;
Tumpey, Terrence M. .
JOURNAL OF VIROLOGY, 2014, 88 (17) :9647-9654
[5]   Pathogenesis, Transmissibility, and Ocular Tropism of a Highly Pathogenic Avian Influenza A (H7N3) Virus Associated with Human Conjunctivitis [J].
Belser, Jessica A. ;
Davis, C. Todd ;
Balish, Amanda ;
Edwards, Lindsay E. ;
Zeng, Hui ;
Maines, Taronna R. ;
Gustin, Kortney M. ;
Lopez Martinez, Irma ;
Fasce, Rodrigo ;
Cox, Nancy J. ;
Katz, Jacqueline M. ;
Tumpey, Terrence M. .
JOURNAL OF VIROLOGY, 2013, 87 (10) :5746-5754
[6]   Ocular Tropism of Respiratory Viruses [J].
Belser, Jessica A. ;
Rota, Paul A. ;
Tumpey, Terrence M. .
MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS, 2013, 77 (01) :144-156
[7]   Influenza Virus Respiratory Infection and Transmission Following Ocular Inoculation in Ferrets [J].
Belser, Jessica A. ;
Gustin, Kortney M. ;
Maines, Taronna R. ;
Pantin-Jackwood, Mary J. ;
Katz, Jacqueline M. ;
Tumpey, Terrence M. .
PLOS PATHOGENS, 2012, 8 (03) :e1002569
[8]   Oseltamivir Inhibits H7 Influenza Virus Replication in Mice Inoculated by the Ocular Route [J].
Belser, Jessica A. ;
Sleeman, Katrina ;
Pearce, Melissa B. ;
Katz, Jacqueline M. ;
Gubareva, Larisa V. ;
Tumpey, Terrence M. .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2012, 56 (03) :1616-1618
[9]   Ocular Tropism of Influenza A Viruses: Identification of H7 Subtype-Specific Host Responses in Human Respiratory and Ocular Cells [J].
Belser, Jessica A. ;
Zeng, Hui ;
Katz, Jacqueline M. ;
Tumpey, Terrence M. .
JOURNAL OF VIROLOGY, 2011, 85 (19) :10117-10125
[10]   The ferret as a model organism to study influenza A virus infection [J].
Belser, Jessica A. ;
Katz, Jacqueline M. ;
Tumpey, Terrence M. .
DISEASE MODELS & MECHANISMS, 2011, 4 (05) :575-579