Correlation Between the Interval of Influenza Virus Infectivity and Results of Diagnostic Assays in a Ferret Model

Inagaki, Kengo; Song, Min‐Suk; Crumpton, Jeri‐Carol; DeBeauchamp, Jennifer; Jeevan, Trushar; Tuomanen, Elaine; Webby, Richard J.; Hakim, Hana

doi:10.1093/infdis/jiv331

Cited by 23 publications

(21 citation statements)

References 15 publications

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“…The link between 'PCR-negativity' and 'end of infectiousness' is not well established but noninfective influenza nucleic acids remain detectable by PCR after viral culture becomes negative, and animal models suggest that it is viral culture that correlates best with the presence of infective virions [19]. PCR-negativity is therefore likely to over-estimate, not underestimate, infectivity.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Implementation of influenza point-of-care testing and patient cohorting during a high-incidence season: a retrospective analysis of impact on infection prevention and control and clinical outcomes

Youngs

Marshall

Farragher

et al. 2019

Journal of Hospital Infection

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Section: Accepted Manuscriptmentioning

confidence: 99%

Implementation of influenza point-of-care testing and patient cohorting during a high-incidence season: a retrospective analysis of impact on infection prevention and control and clinical outcomes

Youngs

Marshall

Farragher

et al. 2019

Journal of Hospital Infection

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“…In fact, real-time reverse transcriptase PCR results remained positive 6-8 days after the loss of transmissibility. 10 For SARS coronavirus, viral RNA is detectable in the respiratory secretions and stools of some patients after onset of illness for more than 1 month, but live virus could not be detected by culture after week 3. 11 The inability to differentiate between infective and noninfective (dead or antibody-neutralised) viruses remains a major limitation of nucleic acid detection.…”

mentioning

confidence: 99%

Understanding COVID-19: what does viral RNA load really mean?

Joynt

2020

The Lancet Infectious Diseases

120

111

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“…S1 in the supplemental material). However, we note that quantitation of viral RNA species is not a clear indicator of either infectious virus or shedding of transmissible virus (45).…”

Section: In Vivomentioning

confidence: 74%

The PA Endonuclease Inhibitor RO-7 Protects Mice from Lethal Challenge with Influenza A or B Viruses

Jones

Marathe

Vogel

et al. 2017

Antimicrob Agents Chemother

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Current influenza treatment relies on a single class of antiviral drugs, the neuraminidase inhibitors (NAIs), raising concern over the potential emergence of resistant variants and necessitating the development of novel drugs. In recent years, investigational inhibitors targeting the endonuclease activity of the influenza acidic polymerase (PA) protein have yielded encouraging results, although there are only limited data on their in vivo efficacy. Here, we examined the antiviral potential of the PA endonuclease inhibitor RO-7 in prophylactic and therapeutic regimens in BALB/c mice inoculated with influenza A/California/04/2009 (H1N1)pdm09 or B/Brisbane/60/2008 viruses, which represent currently circulating antigenic variants. RO-7 was administered to mice intraperitoneally twice daily at dosages of 6, 15, or 30 mg/ kg/day for 5 days, starting 4 h before or 24 or 48 h after virus inoculation, and showed no adverse effects. Prophylactic administration completely protected mice from lethal infection by influenza A or B virus. The level of therapeutic protection conferred depended upon the time of treatment initiation and RO-7 dosage, resulting in 60 to 100% and 80 to 100% survival with influenza A and B viruses, respectively. RO-7 treatment significantly decreased virus titers in the lung and lessened the extent and severity of lung damage. No PA endonuclease-inhibitor resistance was observed in viruses isolated from lungs of RO-7-treated mice, and the viruses remained susceptible to the drug at nanomolar concentrations in phenotypic assays. These in vivo efficacy results further highlight the potential of RO-7 for development as antiviral therapy for influenza A and B virus infections.

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Correlation Between the Interval of Influenza Virus Infectivity and Results of Diagnostic Assays in a Ferret Model

Abstract: Antigen-detection testing and virus culture but not real-time RT-PCR identified the end of the infectious period.

Cited by 23 publications

References 15 publications

Implementation of influenza point-of-care testing and patient cohorting during a high-incidence season: a retrospective analysis of impact on infection prevention and control and clinical outcomes

Implementation of influenza point-of-care testing and patient cohorting during a high-incidence season: a retrospective analysis of impact on infection prevention and control and clinical outcomes

Understanding COVID-19: what does viral RNA load really mean?

The PA Endonuclease Inhibitor RO-7 Protects Mice from Lethal Challenge with Influenza A or B Viruses

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