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

Belser, Jessica A.; Maines, Taronna R.; Creager, Hannah M.; Katz, Jacqueline M.; Tumpey, Terrence M.

doi:10.1016/j.virol.2015.06.020

Cited by 16 publications

(15 citation statements)

References 39 publications

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“…H7 subtype viruses in cases presenting with conjunctivitis have been confirmed in either respiratory samples or eye swabs, although eye swabs are more frequently positive than throat swabs (by either RT-PCR or virus culture), with most cases detected within the first 4–5 days after illness onset. 15,16 In support of antiviral treatment of influenza virus-associated conjunctivitis (table 1), efficacy of the neuraminidase inhibitor oseltamivir following ocular inoculation of mice or ferrets with influenza viruses has been shown to reduce viral replication and limit virus transmissibility, 40,41 but further study is needed regarding the bioavailability of oseltamivir to the eye and use of antiviral agents when conjunctivitis is the primary manifestation of PCR-confirmed influenza and co-infection with other potential pathogens has been ruled out.…”

Section: The Eye Is Susceptible To Avian and Human Influenza Virus Inmentioning

confidence: 99%

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The eyes have it: influenza virus infection beyond the respiratory tract

Belser

Lash

Garg

et al. 2018

The Lancet Infectious Diseases

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Avian and human influenza A viruses alike have shown a capacity to use the eye as a portal of entry and cause ocular disease in human beings. However, whereas influenza viruses generally represent a respiratory pathogen and only occasionally cause ocular complications, the H7 virus subtype stands alone in possessing an ocular tropism. Clarifying what confers such non-respiratory tropism to a respiratory virus will permit a greater ability to identify, treat, and prevent zoonotic human infection following ocular exposure to influenza viruses; especially those within the H7 subtype, which continue to cause avian epidemics on many continents.

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Section: The Eye Is Susceptible To Avian and Human Influenza Virus Inmentioning

confidence: 99%

“…Experimental data previously published. 40,42 ‡ Number of infected ferrets/total number of inoculated ferrets, as determined by the presence of infectious virus in nasal wash specimens collected days 1–7 post inoculation. …”

Section: Figurementioning

confidence: 99%

The eyes have it: influenza virus infection beyond the respiratory tract

Belser

Lash

Garg

et al. 2018

The Lancet Infectious Diseases

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“…For aerosol inhalation inoculation experiments, ferrets were exposed to a high dose (10 5.7 EID 50 ) or a low dose (10 3.5 EID 50 ) of H7N2 virus as described previously (19). For concurrent ocular-aerosol inhalation inoculation, ferrets were exposed to a range of doses (10 2.9 to 10 3.6 EID 50 ) of H7N2 virus as described previously (21,22). All virus-inoculated ferrets were observed daily for clinical signs and symptoms of infection, with nasal wash (NW), conjunctival wash (CW), and rectal swab (RS) specimens being collected on alternate days p.i.…”

Section: Virusesmentioning

confidence: 99%

“…In addition to the inhalation of virus-containing aerosols, our laboratory has shown previously that ferrets may become productively infected with influenza virus following an ocular-only aerosol exposure or concurrent ocular-aerosol inhalation exposure (21,22). This work has revealed that very low levels of exposure of the ocular surface to aerosols can result in a productive respiratory infection in mammals, with heightened replication occurring when mammals are infected with aerosolized virus via both the ocular and respiratory routes.…”

mentioning

confidence: 97%

A Novel A(H7N2) Influenza Virus Isolated from a Veterinarian Caring for Cats in a New York City Animal Shelter Causes Mild Disease and Transmits Poorly in the Ferret Model

Belser

Pulit-Penaloza

Sun

et al. 2017

J Virol

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In December 2016, a low-pathogenic avian influenza (LPAI) A(H7N2) virus was identified to be the causative source of an outbreak in a cat shelter in New York City, which subsequently spread to multiple shelters in the states of New York and Pennsylvania. One person with occupational exposure to infected cats became infected with the virus, representing the first LPAI H7N2 virus infection in a human in North America since 2003. Considering the close contact that frequently occurs between companion animals and humans, it was critical to assess the relative risk of this novel virus to public health. The virus isolated from the human case, A/New York/108/2016 (NY/108), caused mild and transient illness in ferrets and mice but did not transmit to naive cohoused ferrets following traditional or aerosol-based inoculation methods. The environmental persistence of NY/108 virus was generally comparable to that of other LPAI H7N2 viruses. However, NY/108 virus replicated in human bronchial epithelial cells with an increased efficiency compared with that of previously isolated H7N2 viruses. Furthermore, the novel H7N2 virus was found to utilize a relatively lower pH for hemagglutinin activation, similar to human influenza viruses. Our data suggest that the LPAI H7N2 virus requires further adaptation before representing a substantial threat to public health. However, the reemergence of an LPAI H7N2 virus in the northeastern United States underscores the need for continuous surveillance of emerging zoonotic influenza viruses inclusive of mammalian species, such as domestic felines, that are not commonly considered intermediate hosts for avian influenza viruses. IMPORTANCE Avian influenza viruses are capable of crossing the species barrier to infect mammals, an event of public health concern due to the potential acquisition of a pandemic phenotype. In December 2016, an H7N2 virus caused an outbreak in cats in multiple animal shelters in New York State. This was the first detection of this virus in the northeastern United States in over a decade and the first documented infection of a felid with an H7N2 virus. A veterinarian became infected following occupational exposure to H7N2 virus-infected cats, necessitating the evaluation of this virus for its capacity to cause disease in mammals. While the H7N2 virus was associated with mild illness in mice and ferrets and did not spread well between ferrets, it nonetheless possessed several markers of virulence for mammals. These data highlight the promiscuity of influenza viruses and the need for diligent surveillance across multiple species to quickly identify an emerging strain with pandemic potential.

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“…M2 ion channel blockers, with potential neurotoxicity, inhibits influenza A virus only8. NAIs act by binding to the active site of the viral NA to prevent release and spread of progeny virions from infected cells during the replication cycle1, which is a promising target for anti-influenza drugs screening9. However, several strains were reported to be resistant to oseltamivir due to mutations in the viral amino acid sequence1011.…”

mentioning

confidence: 99%

Antiviral activity of chlorogenic acid against influenza A (H1N1/H3N2) virus and its inhibition of neuraminidase

Ding

Cao

et al. 2017

Sci Rep

151

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Lonicera japonica Thunb, rich in chlorogenic acid (CHA), is used for viral upper respiratory tract infection treatment caused by influenza virus, parainfluenza virus, and respiratory syncytial virus, ect in China. It was reported that CHA reduced serum hepatitis B virus level and death rate of influenza virus-infected mice. However, the underlying mechanisms of CHA against the influenza A virus have not been fully elucidated. Here, the antiviral effects and potential mechanisms of CHA against influenza A virus were investigated. CHA revealed inhibitory against A/PuertoRico/8/1934(H1N1) (EC50 = 44.87 μM), A/Beijing/32/92(H3N2) (EC50 = 62.33 μM), and oseltamivir-resistant strains. Time-course analysis showed CHA inhibited influenza virus during the late stage of infectious cycle. Indirect immunofluorescence assay indicated CHA down-regulated the NP protein expression. The inhibition of neuraminidase activity confirmed CHA blocked release of newly formed virus particles from infected cells. Intravenous injection of 100 mg/kg/d CHA possessed effective antiviral activity in mice, conferring 60% and 50% protection from death against H1N1 and H3N2, reducing virus titres and alleviating inflammation in the lungs effectively. These results demonstrate that CHA acts as a neuraminidase blocker to inhibit influenza A virus both in cellular and animal models. Thus, CHA has potential utility in the treatment of the influenza virus infection.

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

Cited by 16 publications

References 39 publications

The eyes have it: influenza virus infection beyond the respiratory tract

The eyes have it: influenza virus infection beyond the respiratory tract

A Novel A(H7N2) Influenza Virus Isolated from a Veterinarian Caring for Cats in a New York City Animal Shelter Causes Mild Disease and Transmits Poorly in the Ferret Model

Antiviral activity of chlorogenic acid against influenza A (H1N1/H3N2) virus and its inhibition of neuraminidase

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