High #prevalence of #SARS‐CoV‐2 and #influenza A virus (#H1N1) #coinfection in dead patients in Northeastern #Iran (J Med Virol., abstract)

[Source: Journal of Medical Virology, full page: (LINK). Abstract, edited.]

High prevalence of SARS‐CoV‐2 and influenza A virus (H1N1) co‐infection in dead patients in Northeastern Iran

Seyed Ahmad Hashemi MD,  Saghar Safamanesh MSc,  Hamed Ghasem Zadeh‐moghaddam,  Majid Ghafouri MD,  Azimian Amir PhD

First published: 28 July 2020 | DOI:  https://doi.org/10.1002/jmv.26364

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/jmv.26364

 

Abstract

In the last months of 2019, an outbreak of fatal respiratory disease started in Wuhan, China, and quickly spread to other parts of the world. It named COVID‐19, and to date, thousands of cases of infection and death reported worldwide. The disease is associated with a wide range of symptoms that make it difficult to diagnose it accurately. The previous SARS pandemic in 2003, researchers found that the patients with fever, cough, or sore throat had a 5% influenza virus‐positive rate. This finding sparked in our minds that the wide range of symptoms and also relatively high prevalence of death in our patients may be due to the co‐infection with other viruses. Thus, we evaluate the co‐infection of SARS‐CoV‐2 with other respiratory viruses in dead patients in North Khorasan. We evaluated the presence of influenza A/B virus, Human metapneumovirus, bocavirus, adenovirus, respiratory syncytial virus, and parainfluenza viruses in 105 SARS‐CoV‐2 positive dead patients, using PCR and RT‐PCR tests. We found co‐infection with influenza virus in 22.3%, respiratory syncytial virus, and bocavirus in 9.7%, parainfluenza viruses in 3.9%, Human metapneumovirus in 2.9% and finally adenovirus in 1.9% of SARS‐CoV‐2 positive dead cases.

The highlights of our findings are a high prevalence of co‐infection with influenza A virus and the monopoly of co‐infection with Human metapneumovirus in children.

This article is protected by copyright. All rights reserved.

Keywords: SARS-CoV-2; COVID-19; Seasonal Influenza; H1N1pdm09; Metapneumovirus; Iran.

——

#Global #seasonality of #human seasonal #coronaviruses: a clue for post-pandemic circulating season of #SARS-CoV-2 virus? (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Global seasonality of human seasonal coronaviruses: a clue for post-pandemic circulating season of SARS-CoV-2 virus?

You Li, Xin Wang, Harish Nair

The Journal of Infectious Diseases, jiaa436, https://doi.org/10.1093/infdis/jiaa436

Published: 21 July 2020

 

Abstract

Background

The ongoing pandemic of Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 virus could recur as seasonal outbreaks, a circulating pattern observed among other pre-existing human seasonal coronaviruses (sCoV). However, little is known about seasonality of sCoV on a global scale.

Methods

We conducted a systematic review of data on seasonality of sCoV. We compared seasonality of sCoV with influenza virus and respiratory syncytial virus. We modelled monthly activity of sCoV using site-specific weather data.

Results

We included sCoV seasonality data in 40 sites from 21 countries. SCoV was prevalent in winter months in most temperate sites except for China while sCoV tended to be less seasonal in China and in tropical sites. In temperate sites excluding China, 53.1% of annual sCoV cases (Interquartile range, IQR: 34.6–61.9) occurred during influenza season and 49.6% (IQR: 30.2–60.2) of sCoV occurred during respiratory syncytial virus season. Low temperature combined with high relative humidity was associated with higher sCoV activity.

Conclusions

This is the first study that provides an overview of the global seasonality of sCoV. Our findings offer clues to the possible post-pandemic circulating season of SARS-CoV-2 and add to the knowledge pool necessary for post-pandemic preparedness for SARS-CoV-2.

COVID-19, SARS-CoV-2, seasonality, human coronavirus, temperature, relative humidity

Issue Section: Major Article

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© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: SARS-CoV-2; COVID-19; Coronavirus; RSV; Seasonal Influenza.

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#Baloxavir Marboxil for #Prophylaxis against #Influenza in #Household Contacts (N Engl J Med., abstract)

[Source: The New England Journal of Medicine, full page: (LINK). Abstract, edited.]

Baloxavir Marboxil for Prophylaxis against Influenza in Household Contacts

Hideyuki Ikematsu, M.D., Frederick G. Hayden, M.D., Keiko Kawaguchi, M.S., Masahiro Kinoshita, M.Pharm., Menno D. de Jong, M.D., Nelson Lee, M.D., Satoru Takashima, M.S., Takeshi Noshi, M.S., Kenji Tsuchiya, M.S., and Takeki Uehara, Ph.D.

 

Abstract

BACKGROUND

Baloxavir marboxil (baloxavir) is a polymerase acidic protein (PA) endonuclease inhibitor with clinical efficacy in the treatment of uncomplicated influenza, including in outpatients at increased risk for complications. The postexposure prophylactic efficacy of baloxavir in the household setting is unclear.

METHODS

We conducted a multicenter, double-blind, randomized, placebo-controlled trial to evaluate the postexposure prophylactic efficacy of baloxavir in household contacts of index patients with confirmed influenza during the 2018–2019 season in Japan. The participants were assigned in a 1:1 ratio to receive either a single dose of baloxavir or placebo. The primary end point was clinical influenza, as confirmed by reverse-transcriptase–polymerase-chain-reaction testing, over a period of 10 days. The occurrence of baloxavir-selected PA substitutions associated with reduced susceptibility was assessed.

RESULTS

A total of 752 household contacts of 545 index patients were randomly assigned to receive baloxavir or placebo. Among the index patients, 95.6% had influenza A virus infection, 73.6% were younger than 12 years of age, and 52.7% received baloxavir. Among the participants who could be evaluated (374 in the baloxavir group and 375 in the placebo group), the percentage in whom clinical influenza developed was significantly lower in the baloxavir group than in the placebo group (1.9% vs. 13.6%) (adjusted risk ratio, 0.14; 95% confidence interval [CI], 0.06 to 0.30; P<0.001). Baloxavir was effective in high-risk, pediatric, and unvaccinated subgroups of participants. The risk of influenza infection, regardless of symptoms, was lower with baloxavir than with placebo (adjusted risk ratio, 0.43; 95% CI, 0.32 to 0.58). The incidence of adverse events was similar in the two groups (22.2% in the baloxavir group and 20.5% in the placebo group). In the baloxavir group, the viral PA substitutions I38T/M or E23K were detected in 10 (2.7%) and 5 (1.3%) participants, respectively. No transmission of these variants from baloxavir-treated index patients to participants in the placebo group was detected; however, several instances of transmission to participants in the baloxavir group could not be ruled out.

CONCLUSIONS

Single-dose baloxavir showed significant postexposure prophylactic efficacy in preventing influenza in household contacts of patients with influenza. (Funded by Shionogi; Japan Primary Registries Network number, JapicCTI-184180.)

Keywords: Seasonal Influenza; Antivirals; Baloxavir.

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#Analysis of #Covid19 and non-Covid-19 viruses, including #influenza viruses, to determine the influence of intensive preventive measures in #Japan (J Clin Virol., abstract)

[Source: Journal of Clinical Virology, full page: (LINK). Abstract, edited.]

Journal of Clinical Virology | Available online 7 July 2020, 104543 | In Press, Journal Pre-proof | Short communication

Analysis of Covid-19 and non-Covid-19 viruses, including influenza viruses, to determine the influence of intensive preventive measures in Japan

Yosuke Hirotsu a, Makoto Maejim a,b, Masahiro Shibusawa b, Kenji Amemiya c, Yuki Nagakubo b,c, Kazuhiro Hosaka b, Hitomi Sueki b, Hitoshi Mochizuki a,d, Toshiharu Tsutsui e, Yumiko Kakizaki e, Yoshihiro Miyashita e, Masao Omata d,f

a Genome Analysis Center, Japan; b Division of Microbiology in Clinical Laboratory, Japan; c Division of Genetics and Clinical Laboratory, Japan; d Department of Gastroenterology, Japan; e Lung Cancer and Respiratory Disease Center, Yamanashi Central Hospital, 1-1-1 Fujimi, Kofu, Yamanashi, Japan; f The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan

Received 4 June 2020, Revised 3 July 2020, Accepted 6 July 2020, Available online 7 July 2020.

DOI: https://doi.org/10.1016/j.jcv.2020.104543

 

Highlights

  • The prevalence of infected patients with SARS-CoV-2 or other viruses is unknown
  • We analyzed SARS-CoV-2 and 17 viruses in 191 patients with cold-like symptom in Japan
  • 21% of patient (n = 40) was infected at least one virus, including SARS-CoV-2 (n = 8)
  • No influenza virus was observed in this study
  • The data implies different infectivity between influenza and SARS-CoV2

 

Abstract

Background

Severe acute respiratory coronavirus 2 (SARS-CoV-2) has spread and caused death worldwide. Preventive measures and infection control are underway, and some areas show signs of convergence. Other viruses in addition to SARS-CoV-2 cause cold-like symptoms and spread in the winter. However, the extent to which SARS-CoV-2, influenza viruses and other causative viruses have prevailed since implementing preventive measures is unclear.

Objectives

We aim to investigate the incidence of causative viruses and pathogens in patients.

Study design

We collected 191 nasopharyngeal swabs from patients with cold-like symptoms in Japan. All samples were subjected to multiplex PCR with the FilmArray Respiratory Panel and reverse transcription PCR (RT-PCR) to detect SARS-CoV-2.

Results

FilmArray Respiratory Panel analysis detected at least one virus in 32 of 191 patients with cold-like symptoms (21%). Of these, we frequently identified human rhinoviruses/enteroviruses (5.8%, n=11), human metapneumovirus (3.7%, n=7), coronavirus 229E (2.1%, n=4) and coronavirus OC43 (1.6%, n=3); while no influenza viruses were detected. RT-PCR analysis detected SARS-CoV-2 (4.2%, n=8) in patients who were not infected with the aforementioned respiratory viruses.

Conclusions

Co-infection with SARS-CoV-2 and other viruses was not observed. Causative viruses remain prevalent after implementing preventive measures. SARS-CoV-2 differs from influenza viruses in its infectivity.

© 2020 Elsevier B.V. All rights reserved.

Keywords: SARS-CoV-2; COVID-19; Seasonal Influenza; Enterovirus; Rhinovirs; Metapneumovirus; Diagnostic tests.

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Successful #Treatment With #Baloxavir Marboxil of a Patient With #Peramivir #Resistant #Influenza A / #H3N2 With a Dual E119D/R292K Substitution After Allogeneic Hematopoietic Cell #Transplantation: A Case Report (BMC Infect Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

BMC Infect Dis. 2020 Jul 6;20(1):478. doi: 10.1186/s12879-020-05205-1.

Successful Treatment With Baloxavir Marboxil of a Patient With Peramivir-Resistant Influenza A/H3N2 With a Dual E119D/R292K Substitution After Allogeneic Hematopoietic Cell Transplantation: A Case Report

Naonori Harada 1, Wataru Shibata 2 3, Hideo Koh 4, Emi Takashita 5, Seiichiro Fujisaki 5, Hiroshi Okamura 1, Satoru Nanno 1, Koichi Yamada 2 3, Hirohisa Nakamae 1, Masayuki Hino 1, Hiroshi Kakeya 2 3

Affiliations: 1 Hematology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan. 2 Department of Infection Control Science, Graduate School of Medicine, Osaka City University, Osaka, Japan. 3 Research Center for Infectious Disease Sciences (RCIDS), Graduate School of Medicine, Osaka City University, Osaka, Japan. 4 Hematology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan. hide_koh@med.osaka-cu.ac.jp. 5 Influenza Virus Research Center, National Institute of Infectious Diseases, Tokyo, Japan.

PMID: 32631240 DOI: 10.1186/s12879-020-05205-1

 

Abstract

Background:

Extended use of oseltamivir in an immunocompromised host could reportedly induce neuraminidase gene mutation possibly leading to oseltamivir-resistant influenza A/H3N2 virus. To our knowledge, no report is available on the clinical course of a severely immunocompromised patient with a dual E119D/R292K neuraminidase mutated-influenza A/H3N2 during the administration of peramivir.

Case presentation:

A 49-year-old male patient was admitted for second allogeneic hematopoietic cell transplantation for active acute leukemia. The patient received 5 mg prednisolone and 75 mg cyclosporine and had severe lymphopenia (70/μL). At the time of hospitalization, the patient was diagnosed with upper tract influenza A virus infection, and oseltamivir treatment was initiated immediately. However, the patient was intolerant to oseltamivir. The following day, treatment was changed to peramivir. Despite a total period of neuraminidase-inhibitor administration of 16 days, the symptoms and viral shedding continued. Changing to baloxavir marboxil resolved the symptoms, and the influenza diagnostic test became negative. Subsequently, sequence analysis of the nasopharyngeal specimen revealed the dual E119D/R292K neuraminidase mutant influenza A/H3N2.

Conclusions:

In a highly immunocompromised host, clinicians should take care when peramivir is used for extended periods to treat influenza virus A/H3N2 infection as this could potentially leading to a dual E119D/R292K substitution in neuraminidase protein. Baloxavir marboxil may be one of the agents that can be used to treat this type of mutated influenza virus infection.

Keywords: Allogeneic hematopoietic cell transplantation; Baloxavir marboxil; Dual E119D/R292K substitution; Immunocompromised host; Influenza A/H3N2; Neuraminidase mutation; Peramivir resistance.

Keywords: Seasonal Influenza; Antivirals; Drugs Resistance; Hematology; H3N2; Cancer; Immunosuppression; Peramivir; Baloxavir.

—–

Characterization of #Neuraminidase #Inhibitor #Resistant #Influenza Virus Isolates From Immunocompromised Patients in the Republic of #Korea (Virol J., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Virol J. 2020 Jul 6;17(1):94. doi: 10.1186/s12985-020-01375-1.

Characterization of Neuraminidase Inhibitor-Resistant Influenza Virus Isolates From Immunocompromised Patients in the Republic of Korea

Heui Man Kim 1, Namjoo Lee 1, Mi-Seon Kim 1, Chun Kang 1, Yoon-Seok Chung 2

Affiliations: 1 Division of Viral Diseases, Center for Laboratory Control of Infectious Diseases, Korea Centers for Disease Control and Prevention, Cheongju-si, South Korea. 2 Division of Viral Diseases, Center for Laboratory Control of Infectious Diseases, Korea Centers for Disease Control and Prevention, Cheongju-si, South Korea. rollstone93@korea.kr.

PMID: 32631440 DOI: 10.1186/s12985-020-01375-1

 

Abstract

Background:

The emergence of influenza viruses resistant to anti-influenza drugs is a threat to global public health. The Korea Centers for Disease Control and Prevention operates the Korea Influenza and Respiratory Viruses Surveillance System (KINRESS) to monitor epidemics of influenza and Severe Acute Respiratory Infection (SARI) to identify mutated influenza viruses affecting drug resistance, pathogenesis, and transmission.

Methods:

Oropharyngeal swab samples were collected from KINRESS and SARI during the 2018-2019 season. The specimens confirmed influenza virus using real-time RT-PCR on inoculated MDCK cells. HA and NA sequences of the influenza viruses were analyzed for phylogeny and mutations. Neuraminidase inhibition and hemagglutination inhibition assays were utilized to characterize the isolates.

Results:

Two A(H1N1)pdm09 isolates harboring an H275Y substitution in the neuraminidase sequence were detected in patients with acute hematologic cancer. They had prolonged respiratory symptoms, with the virus present in the respiratory tract despite oseltamivir and peramivir treatment. Through the neuraminidase inhibition assay, both viruses were found to be resistant to oseltamivir and peramivir, but not to zanamivir. Although hemagglutinin and neuraminidase phylogenetic analyses suggested that the 2 A(H1N1)pdm09 isolates were not identical, their antigenicity was similar to that of the 2018-19 influenza vaccine virus.

Conclusions:

Our data indicate the utility of monitoring influenza-infected immunocompromised patients in general hospitals for the early detection of emerging neuraminidase inhibitor-resistant viruses and maintaining continuous laboratory surveillance of patients with influenza-like illness in sentinel clinics to monitor the spread of such new variants. Finally, characterization of the virus can inform the risk assessment for future epidemics and pandemics caused by drug-resistant influenza viruses.

Keywords: Drug resistance; H275Y; Immunocompromised patients; Influenza virus.

Keywords: Seasonal Influenza; H1N1pdm09; Cancer; Immunosuppression; Antivirals; Drugs Resistance; Oseltamivir; Zanamivir; Peramivir; S. Korea.

——

#Monoclonal #Antibody #Therapy Protects Pharmacologically Immunosuppressed Mice from #Lethal Infection with #Influenza B Virus (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Monoclonal Antibody Therapy Protects Pharmacologically Immunosuppressed Mice from Lethal Infection with Influenza B Virus

Bindumadhav M. Marathe, Guha Asthagiri Arunkumar, Peter Vogel, Philippe Noriel Q. Pascua, Jeremy Jones, Richard J. Webby, Florian Krammer, Elena A. Govorkova

DOI: 10.1128/AAC.00284-20

 

ABSTRACT

Human influenza A and B viruses are highly contagious and cause similar illnesses and seasonal epidemics. Currently available antiviral drugs have limited efficacy in humans with compromised immune systems; therefore, alternative strategies for protection are needed. Here, we investigated whether monoclonal antibodies (mAbs) targeting hemagglutinin (HA) and/or neuraminidase (NA) proteins would protect immunosuppressed mice from severe infections with influenza B virus. Pharmacologically immunosuppressed BALB/c mice were inoculated with B/Brisbane/60/2008 (BR/08) influenza virus and were treated with a single dose of 1, 5, or 25 mg/kg/day of either an anti-HA mAb (1D2) or an anti-NA mAb (1F2) starting at 24 hours post inoculation (hpi). Monotherapy with 1D2 or 1F2 mAbs provided dose-dependent protection of mice, with decreased BR/08 virus replication and spread in the mouse lungs, as compared to those of controls. Combination treatment with 1D2 and 1F2 provided greater protection than did monotherapy, even when started at 48 hpi. Virus spread was also efficiently restrained within the lungs, being limited to 6%, 10%, and 10% of that seen in active infection when treatment was initiated at 24, 48, and 72 hpi, respectively. In most cases, the expression of cytokines and chemokines was altered according to when treatment was initiated. Higher expression of pro-inflammatory IP-10 and MCP-1 in combination-treatment groups, but not in monotherapy groups, to some extent, promoted better control of virus spread within the lungs. This study demonstrates the potential value of mAb immunotherapy in treating influenza in immunocompromised hosts who are at increased risk of severe disease.

Copyright © 2020 American Society for Microbiology. All Rights Reserved.

Keywords: Seasonal Influenza; Influenza B; Monoclonal Antibodies; Animal models.

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#Lopinavir / #ritonavir is associated with #pneumonia #resolution in #COVID19 patients with #influenza #coinfection: a retrospective matched‐pair cohort study (J Med Virol., abstract)

[Source: Journal of Medical Virology, full page: (LINK). Abstract, edited.]

Lopinavir/ritonavir is associated with pneumonia resolution in COVID‐19 patients with influenza coinfection: a retrospective matched‐pair cohort study

Chong Yu,  Zhiguo Zhang,  Yujiao Guo,  Jing Shi,  Guangchang Pei,  Ying Yao,  Wenhui Liao,  Rui Zeng

First published: 04 July 2020 | DOI:  https://doi.org/10.1002/jmv.26260

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/jmv.26260

 

Abstract

Background

During the early stages of the pandemic, some coronavirus disease (COVID‐19)patients were misdiagnosed as having influenza, which aroused the concern that some deaths attributed to influenza were actually COVID‐19‐related. Howerver, little is known about whether coinfection with influenza contributes to severity of COVID‐19 pneumonia, and the optimal therapeutic strategy for these patients.

Methods

We retrospectively studied 128 hospitalized patients with COVID‐19 pneumonia. All patients were positive severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)positive by nucleic acid detection. 64 cases were co‐infected with influenza A/B and the other 64 were influenza negative, matched by age, sex, and days from onset of symptoms.

Results

Among the 64 co‐infected patients, 54 (84.4%) were co‐infected with influenza A, and 10 (15.6%) with influenza B. The median duration of viral shedding time from admission was longer for patients with influenza coinfection (17.0 days) than for those without influenza coinfection (12.0 days) (P <0.001). The multivariable Cox proportional hazards model showed that the hazard ratio HR of resolution in lung involvement was 1.878 (P =0.020) for patients administered lopinavir/ritonavir, compared with those not administered lopinavir/ritonavir (95% confidence interval (CI) 1.103, 3.196). Among influenza co‐infected patients, those treated with lopinavir/ritonavir exhibited faster pneumonia resolution within two weeks after symptom onset (37% vs 1%, P =0.001).

Conclusions

There was no difference in lung involvement between influenza co‐infected and non‐infected groups. Lopinavir/ritonavir eliminated the difference of lung involvement between influenza co‐infected and non‐infected groups, indicating that lopinavir/ritonavir is associated with pneumonia resolution in COVID‐19.

This article is protected by copyright. All rights reserved.

Keywords: SARS-CoV-2; COVID-19; Antivirals; Lopinavir; Ritonavir; Seasonal Influenza.

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#Neuraminidase #antigenic #drift of #H3N2 clade 3c.2a viruses alters virus #replication, enzymatic activity and inhibitory #antibody binding (PLOS Pathog., abstract)

[Source: PLOS Pathogens, full page: (LINK). Abstract, edited.]

OPEN ACCESS |  PEER-REVIEWED | RESEARCH ARTICLE

Neuraminidase antigenic drift of H3N2 clade 3c.2a viruses alters virus replication, enzymatic activity and inhibitory antibody binding

Harrison Powell, Andrew Pekosz

Published: June 29, 2020 | DOI: https://doi.org/10.1371/journal.ppat.1008411 | This is an uncorrected proof.

 

Abstract

In the 2014–2015 influenza season a novel neuraminidase (NA) genotype was detected in global human influenza A surveillance. This novel genotype encoded an N-linked glycosylation site at position 245–247 in the NA protein from clade 3c.2a H3N2 viruses. In the years following the 2014–2015 season, this novel NA glycosylation genotype quickly dominated the human H3N2 population of viruses. To assess the effect this novel N-linked glycan has on virus fitness and antibody binding, recombinant viruses with (NA Gly+) or without (NA Gly-) the 245 NA glycan were created. Viruses with the 245 NA Gly+ genotype grew to a significantly lower infectious virus titer on primary, differentiated human nasal epithelial cells (hNEC) compared to viruses with the 245 NA Gly- genotype, but growth was similar on immortalized cells. The 245 NA Gly+ blocked human and rabbit monoclonal antibodies that target the enzymatic site from binding to their epitope. Additionally, viruses with the 245 NA Gly+ genotype had significantly lower enzymatic activity compared to viruses with the 245 NA Gly- genotype. Human monoclonal antibodies that target residues near the 245 NA glycan were less effective at inhibiting NA enzymatic activity and virus replication of viruses encoding an NA Gly+ protein compared to ones encoding NA Gly- protein. Additionally, a recombinant H6N2 virus with the 245 NA Gly+ protein was more resistant to enzymatic inhibition from convalescent serum from H3N2-infected humans compared to viruses with the 245 NA Gly- genotype. Finally, the 245 NA Gly+ protected from NA antibody mediated virus neutralization. These results suggest that while the 245 NA Gly+ decreases virus replication in hNECs and decreases enzymatic activity, the 245 NA glycan blocks the binding of monoclonal and human serum NA specific antibodies that would otherwise inhibit enzymatic activity and virus replication.

 

Author summary

Influenza virus infects millions of people worldwide and leads to thousands of deaths and millions in economic loss each year. During the 2014/2015 season circulating human H3N2 viruses acquired a novel mutation in the neuraminidase (NA) protein. This mutation has since fixed in human H3N2 viruses. This mutation at position 245 through 247 in the amino acid sequence of NA encoded an N-linked glycosylation. Here, we studied how this N-linked glycan impacts virus fitness and protein function. We found that this N-linked glycan on the NA protein decreased viral replication fitness on human nasal epithelial cells (hNEC) but not immortalized Madin-Darby Canine Kidney (MDCK) cells. We also determined this glycan decreases NA enzymatic activity, enzyme kinetics and affinity for substrate. Furthermore, we show that this N-linked glycan at position 245 blocks some NA specific inhibitory antibodies from binding to the protein, inhibiting enzymatic activity, and inhibiting viral replication. Finally, we showed that viruses with the novel 245 N-linked glycan are more resistant to convalescent human serum antibody mediated enzymatic inhibition. While this 245 N-linked Glycan decreases viral replication and enzymatic activity, the 245 N-linked glycan protects the virus from certain NA specific inhibitory antibodies. Our study provides new insight into the function of this dominant H3N2 NA mutation and how it impacts antigenicity and fitness of circulating H3N2 viruses.

___

Citation: Powell H, Pekosz A (2020) Neuraminidase antigenic drift of H3N2 clade 3c.2a viruses alters virus replication, enzymatic activity and inhibitory antibody binding. PLoS Pathog 16(6): e1008411. https://doi.org/10.1371/journal.ppat.1008411

Editor: Anice C. Lowen, Emory University School of Medicine, UNITED STATES

Received: February 13, 2020; Accepted: May 11, 2020; Published: June 29, 2020

Copyright: © 2020 Powell, Pekosz. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript.

Funding: The work was supported by CEIRS HHSN272201400007C and T32 AI007417 (HP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Seasonal Influenza; Influenza A; H3N2; Viral pathogenesis.

——

#SARS-CoV-2 does not replicate in embryonated hen’s #eggs or in #MDCK cell lines (Euro Surveill., abstract)

[Source: Eurosurveillance, full page: (LINK). Abstract, edited.]

SARS-CoV-2 does not replicate in embryonated hen’s eggs or in MDCK cell lines

Ian G Barr1,2,3  , Cleve Rynehart1 , Paul Whitney1,2 , Julian Druce4

Affiliations: 1 The WHO Collaborating Centre for Reference and Research on Influenza, The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia; 2 Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia; 3 Faculty of Science and Technology, Federation University, Gippsland, VIC, Australia; 4 Victorian Infectious Diseases Reference Laboratory, The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia

Correspondence:  Ian G Barr

Citation style for this article: Barr Ian G  , Rynehart Cleve , Whitney Paul , Druce Julian . SARS-CoV-2 does not replicate in embryonated hen’s eggs or in MDCK cell lines. Euro Surveill. 2020;25(25):pii=2001122. https://doi.org/10.2807/1560-7917.ES.2020.25.25.2001122

Received: 07 Jun 2020;   Accepted: 25 Jun 2020

 

Abstract

The advent of COVID-19, has posed a risk that human respiratory samples containing human influenza viruses may also contain SARS-CoV-2. This potential risk may lead to SARS-CoV-2 contaminating conventional influenza vaccine production platforms as respiratory samples are used to directly inoculate embryonated hen’s eggs and continuous cell lines that are used to isolate and produce influenza vaccines. We investigated the ability of these substrates to propagate SARS-CoV-2 and found that neither could support SARS-CoV-2 replication.

©  This work is licensed under a Creative Commons Attribution 4.0 International License.

Keywords: SARS-CoV-2; COVID-19; Seasonal Influenza; Vaccines.

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