A 75-year-old woman with seasonal influenza A (H3N2) virus infection and diarrhea

Influenza A (H1N1) viruses of swine origin were introduced into the human population in 2009 and caused a pandemic. The disease burden in the elderly was relatively low, which was attributed to the presence of cross-reacting serum antibodies in this age group, which were raised against seasonal influenza A (H1N1) viruses that circulated before 1957. It has also been described how infection with heterosubtypic influenza viruses can induce some degree of protection against infection by a novel strain of influenza virus. Here, we assess the extent of protective immunity against infection with the 2009 influenza A (H1N1) pandemic influenza virus that is afforded by infection with a seasonal influenza A (H3N2) virus in mice. Mice that experienced a primary A (H3N2) influenza virus infection displayed reduced weight loss after challenge infection and cleared the 2009 influenza A (H1N1) virus infection more rapidly. To elucidate the correlates of protection of this heterosubtypic immunity to pandemic H1N1 virus infection, adoptive transfer experiments were carried out by using selected post-infection lymphocyte populations. Virus-specific CD8+ T-cells in concert with CD4+ T-cells were responsible for the observed protection. These findings may not only provide an explanation for epidemiological differences in the incidence of severe pandemic H1N1 infections, they also indicate that the induction of cross-reactive virus-specific CD8+ and CD4+ T-cell responses may be a suitable approach for the development of universal influenza vaccines.

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Predicting evolution from the shape of genealogical trees

eLife ◽

10.7554/elife.03568 ◽

2014 ◽

Vol 3 ◽

Cited By ~ 94

Author(s):

Richard A Neher ◽

Colin A Russell ◽

Boris I Shraiman

Keyword(s):

Influenza A ◽

Seasonal Influenza ◽

Historical Data ◽

Relative Fitness ◽

H3n2 Virus ◽

Asexual Population ◽

Genealogical Trees ◽

Branching Patterns ◽

Species Specific ◽

Evolution Proceeds

Given a sample of genome sequences from an asexual population, can one predict its evolutionary future? Here we demonstrate that the branching patterns of reconstructed genealogical trees contains information about the relative fitness of the sampled sequences and that this information can be used to predict successful strains. Our approach is based on the assumption that evolution proceeds by accumulation of small effect mutations, does not require species specific input and can be applied to any asexual population under persistent selection pressure. We demonstrate its performance using historical data on seasonal influenza A/H3N2 virus. We predict the progenitor lineage of the upcoming influenza season with near optimal performance in 30% of cases and make informative predictions in 16 out of 19 years. Beyond providing a tool for prediction, our ability to make informative predictions implies persistent fitness variation among circulating influenza A/H3N2 viruses.

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Retraction: Activity of ergoferon against lethal influenza A (H3N2) virus infection in mice

Antiviral Therapy ◽

10.3851/imp3325 ◽

2019 ◽

Vol 24 (3) ◽

pp. 235 ◽

Cited By ~ 1

Author(s):

Maria A Skarnovich ◽

Alexandra G Emelyanova ◽

Nataliia V Petrova ◽

Alena A Borshcheva ◽

Evgeniy A Gorbunov ◽

...

Keyword(s):

Virus Infection ◽

Influenza A ◽

H3n2 Virus

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Phase III Randomized, Double-Blind Study Comparing Single-Dose Intravenous Peramivir with Oral Oseltamivir in Patients with Seasonal Influenza Virus Infection

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00360-11 ◽

2011 ◽

Vol 55 (11) ◽

pp. 5267-5276 ◽

Cited By ~ 73

Author(s):

Shigeru Kohno ◽

Muh-Yong Yen ◽

Hee-Jin Cheong ◽

Nobuo Hirotsu ◽

Tadashi Ishida ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Influenza A ◽

Seasonal Influenza ◽

Influenza Virus Infection ◽

Influenza Viruses ◽

Phase Iii ◽

Controlled Study ◽

Double Blind Study ◽

Double Blind

ABSTRACTAntiviral medications with activity against influenza viruses are important in controlling influenza. We compared intravenous peramivir, a potent neuraminidase inhibitor, with oseltamivir in patients with seasonal influenza virus infection. In a multinational, multicenter, double-blind, double-dummy randomized controlled study, patients aged ≥20 years with influenza A or B virus infection were randomly assigned to receive either a single intravenous infusion of peramivir (300 or 600 mg) or oral administration of oseltamivir (75 mg twice a day [b.i.d.] for 5 days). To demonstrate the noninferiority of peramivir in reducing the time to alleviation of influenza symptoms with hazard model analysis and a noninferiority margin of 0.170, we planned to recruit 1,050 patients in South Korea, Japan, and Taiwan. A total of 1,091 patients (364 receiving 300 mg and 362 receiving 600 mg of peramivir; 365 receiving oseltamivir) were included in the intent-to-treat infected population. The median durations of influenza symptoms were 78.0, 81.0, and 81.8 h in the groups treated with 300 mg of peramivir, 600 mg of peramivir, and oseltamivir, respectively. The hazard ratios of the 300- and 600-mg-peramivir groups compared to the oseltamivir group were 0.946 (97.5% confidence interval [CI], 0.793, 1.129) and 0.970 (97.5% CI, 0.814, 1.157), respectively. Both peramivir groups were noninferior to the oseltamivir group (97.5% CI, <1.170). The overall incidence of adverse drug reactions was significantly lower in the 300-mg-peramivir group, but the incidence of severe reactions in either peramivir group was not different from that in the oseltamivir group. Thus, a single intravenous dose of peramivir may be an alternative to a 5-day oral dose of oseltamivir for patients with seasonal influenza virus infection.

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H3N2 Virus as Causative Agent of ARDS Requiring Extracorporeal Membrane Oxygenation Support

Case Reports in Medicine ◽

10.1155/2014/560208 ◽

2014 ◽

Vol 2014 ◽

pp. 1-3

Author(s):

Adriano Peris ◽

Giovanni Zagli ◽

Pasquale Bernardo ◽

Massimo Bonacchi ◽

Morena Cozzolino ◽

...

Keyword(s):

Intensive Care Unit ◽

Extracorporeal Membrane Oxygenation ◽

Influenza A ◽

Seasonal Influenza ◽

Influenza Season ◽

Influenza Viruses ◽

H3n2 Virus ◽

Membrane Oxygenation ◽

Viral Aetiology ◽

Increased Risk

Pandemic influenza virus A(H1N1) 2009 was associated with a higher risk of viral pneumonia in comparison with seasonal influenza viruses. The influenza season 2011-2012 was characterized by the prevalent circulation of influenza A(H3N2) viruses. Whereas most H3N2 patients experienced mild, self-limited influenza-like illness, some patients were at increased risk for influenza complications because of age or underlying medical conditions. Cases presented were patients admitted to the Intensive Care Unit (ICU) of ECMO referral center (Careggi Teaching Hospital, Florence, Italy). Despite extracorporeal membrane oxygenation treatment (ECMO), one patient with H3N2-induced ARDS did not survive. Our experience suggests that viral aetiology is becoming more important and hospitals should be able to perform a fast differential diagnosis between bacterial and viral aetiology.

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Prolonged intermittent virus shedding during an outbreak of canine influenza A H3N2 virus infection in dogs in three Chicago area shelters: 16 cases (March to May 2015)

Journal of the American Veterinary Medical Association ◽

10.2460/javma.248.9.1022 ◽

2016 ◽

Vol 248 (9) ◽

pp. 1022-1026 ◽

Cited By ~ 12

Author(s):

Sandra Newbury ◽

Jennifer Godhardt-Cooper ◽

Keith P. Poulsen ◽

Francine Cigel ◽

Laura Balanoff ◽

...

Keyword(s):

Virus Infection ◽

Influenza A ◽

H3n2 Virus ◽

Virus Shedding ◽

Chicago Area ◽

Canine Influenza

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Complications and Outcomes of Pandemic 2009 Influenza A (H1N1) Virus Infection in Hospitalized Adults: How Do They Differ From Those in Seasonal Influenza?

The Journal of Infectious Diseases ◽

10.1093/infdis/jir187 ◽

2011 ◽

Vol 203 (12) ◽

pp. 1739-1747 ◽

Cited By ~ 85

Author(s):

N. Lee ◽

P. K. S. Chan ◽

G. C. Y. Lui ◽

B. C. K. Wong ◽

W. W. Y. Sin ◽

...

Keyword(s):

Virus Infection ◽

Influenza A ◽

Seasonal Influenza ◽

H1n1 Virus ◽

Influenza A H1n1 ◽

H1n1 Virus Infection

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Kallikrein-Related Peptidase 5 Contributes to H3N2 Influenza Virus Infection in Human Lungs

Journal of Virology ◽

10.1128/jvi.00421-17 ◽

2017 ◽

Vol 91 (16) ◽

Cited By ~ 7

Author(s):

Mélia Magnen ◽

Fabien Gueugnon ◽

Antoine Guillon ◽

Thomas Baranek ◽

Virginie C. Thibault ◽

...

Keyword(s):

Influenza Virus ◽

Respiratory Tract ◽

Serine Proteases ◽

Lower Respiratory Tract ◽

Influenza A ◽

Seasonal Influenza ◽

Influenza Viruses ◽

H3n2 Virus ◽

Influenza A Viruses

ABSTRACT Hemagglutinin (HA) of influenza virus must be activated by proteolysis before the virus can become infectious. Previous studies indicated that HA cleavage is driven by membrane-bound or extracellular serine proteases in the respiratory tract. However, there is still uncertainty as to which proteases are critical for activating HAs of seasonal influenza A viruses (IAVs) in humans. This study focuses on human KLK1 and KLK5, 2 of the 15 serine proteases known as the kallikrein-related peptidases (KLKs). We find that their mRNA expression in primary human bronchial cells is stimulated by IAV infection. Both enzymes cleaved recombinant HA from several strains of the H1 and/or H3 virus subtype in vitro, but only KLK5 promoted the infectivity of A/Puerto Rico/8/34 (H1N1) and A/Scotland/20/74 (H3N2) virions in MDCK cells. We assessed the ability of treated viruses to initiate influenza in mice. The nasal instillation of only the KLK5-treated virus resulted in weight loss and lethal outcomes. The secretion of this protease in the human lower respiratory tract is enhanced during influenza. Moreover, we show that pretreatment of airway secretions with a KLK5-selective inhibitor significantly reduced the activation of influenza A/Scotland/20/74 virions, providing further evidence of its importance. Differently, increased KLK1 secretion appeared to be associated with the recruitment of inflammatory cells in human airways regardless of the origin of inflammation. Thus, our findings point to the involvement of KLK5 in the proteolytic activation and spread of seasonal influenza viruses in humans. IMPORTANCE Influenza A viruses (IAVs) cause acute infection of the respiratory tract that affects millions of people during seasonal outbreaks every year. Cleavage of the hemagglutinin precursor by host proteases is a critical step in the life cycle of these viruses. Consequently, host proteases that activate HA can be considered promising targets for the development of new antivirals. However, the specific proteases that activate seasonal influenza viruses, especially H3N2 viruses, in the human respiratory tract have remain undefined despite many years of work. Here we demonstrate that the secreted, extracellular protease KLK5 (kallikrein-related peptidase 5) is efficient in promoting the infectivity of H3N2 IAV in vitro and in vivo. Furthermore, we found that its secretion was selectively enhanced in the human lower respiratory tract during a seasonal outbreak dominated by an H3N2 virus. Collectively, our data support the clinical relevance of this protease in human influenza pathogenesis.

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