Early Administration of #Oseltamivir Within 48 Hours After Onset of Flulike Symptoms Can Reduce the #Risk of Influenza B Virus-Associated #Pneumonia in Hospitalized #Pediatric Patients with Influenza B Virus Infection (Pediatr Infect Dis J., abstract)

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

Pediatr Infect Dis J. 2020 Feb;39(2):e20-e22. doi: 10.1097/INF.0000000000002528.

Early Administration of Oseltamivir Within 48 Hours After Onset of Flulike Symptoms Can Reduce the Risk of Influenza B Virus-Associated Pneumonia in Hospitalized Pediatric Patients with Influenza B Virus Infection.

Dai Z1, Zhang L, Yu Q, Liu L, Yang M, Fan K.

Author information: 1 From the Department of Accident and Emergency, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.

 

Abstract

We conducted a retrospective study to identify the risk factors for pneumonia in hospitalized pediatric patients with influenza B infection. Receiving oseltamivir within the first 48 hours of onset and frequent cough was respectively considered as a protective factor and a risk factor for the influenza B virus-associated pneumonia in hospitalized pediatric patients. Early administration of oseltamivir can reduce the risk of influenza B virus-associated pneumonia.

PMID: 31929434 DOI: 10.1097/INF.0000000000002528

Keywords: Seasonal Influenza; Influenza B; Antivirals; Oseltamivir; Pneumonia; Pediatrics.

——

#Encephalitis caused by type B #influenza virus in an adult. Report of one case (Rev Med Chil., abstract)

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

Rev Med Chil. 2019 Jul;147(7):922-927. doi: 10.4067/S0034-98872019000700922.

[Encephalitis caused by type B influenza virus in an adult. Report of one case].

[Article in Spanish]

Reyes C1, Miranda S, Fica A2, Navarrete M3.

Author information: 1 Sub Departamento de Neurología, Hospital Base de Valdivia, Valdivia, Chile. 2 Subdepartamento de Medicina, Hospital Base de Valdivia, Valdivia, Chile. 3 Laboratorio de Biología Molecular, Hospital Base de Valdivia, Valdivia, Chile.

 

Abstract

Neurological manifestations associated with influenza virus infection include encephalitis, encephalopathy, acute necrotizing encephalitis, transverse myelitis, acute disseminated encephalomyelitis, mild encephalitis with reversible splenial syndrome (MERS), and Guillaín Barré syndrome. We report a 16-year-old female who was admitted at our emergency department with seizures, confusion, nystagmus and motor clumsiness five days after an upper a respiratory tract infection. Influenza type B virus infection was confirmed by chain polymerase reaction analysis. The initial electroencephalogram demonstrated a pattern of global slowness without epileptic discharges. One week later, it showed a progression to slow-wave focal bilateral discharges at both temporal and occipital lobes. The patient had a favorable evolution and was discharged 19 days after admission with phenytoin to prevent seizures.

PMID:  31859991 DOI: 10.4067/S0034-98872019000700922

Keywords: Seasonal Influenza; Influenza B; Encephalitis; Neurology.

——

Divergent #evolutionary #trajectories of #influenza B viruses underlie their contemporaneous #epidemic activity (Proc Natl Acad Sci USA, abstract)

[Source: Proceedings of the National Academy of Sciences of the United States of America, full page: (LINK). Abstract, edited.]

Divergent evolutionary trajectories of influenza B viruses underlie their contemporaneous epidemic activity

Ramandeep K. Virk, Jayanthi Jayakumar, Ian H. Mendenhall, Mahesh Moorthy, Pauline Lam, Martin Linster, Julia Lim, Cui Lin, Lynette L. E. Oon, Hong Kai Lee, Evelyn S. C. Koay, Dhanasekaran Vijaykrishna, Gavin J. D. Smith, and Yvonne C. F. Su

PNAS first published December 16, 2019 / DOI: https://doi.org/10.1073/pnas.1916585116

Edited by Peter Palese, Icahn School of Medicine at Mount Sinai, New York, NY, and approved November 18, 2019 (received for review September 25, 2019)

 

Significance

Two influenza B viruses (Victoria and Yamagata) cocirculate in humans and contribute to the estimated 290,000–650,000 annual influenza-attributed deaths. Here, we analysed influenza B genomic data to understand the causes of a recent surge in human influenza B infections. We found that evolution is acting differently on Yamagata and Victoria viruses and that this has led to the cocirculation of a diverse group of influenza B viruses. If this phenomenon continues, we could potentially witness the emergence of 3 or more distinct influenza B viruses that could require their own vaccine component, thereby complicating influenza vaccine formulation and highlighting the urgency of developing universal influenza vaccines.

 

Abstract

Influenza B viruses have circulated in humans for over 80 y, causing a significant disease burden. Two antigenically distinct lineages (“B/Victoria/2/87-like” and “B/Yamagata/16/88-like,” termed Victoria and Yamagata) emerged in the 1970s and have cocirculated since 2001. Since 2015 both lineages have shown unusually high levels of epidemic activity, the reasons for which are unclear. By analyzing over 12,000 influenza B virus genomes, we describe the processes enabling the long-term success and recent resurgence of epidemics due to influenza B virus. We show that following prolonged diversification, both lineages underwent selective sweeps across the genome and have subsequently taken alternate evolutionary trajectories to exhibit epidemic dominance, with no reassortment between lineages. Hemagglutinin deletion variants emerged concomitantly in multiple Victoria virus clades and persisted through epistatic mutations and interclade reassortment—a phenomenon previously only observed in the 1970s when Victoria and Yamagata lineages emerged. For Yamagata viruses, antigenic drift of neuraminidase was a major driver of epidemic activity, indicating that neuraminidase-based vaccines and cross-reactivity assays should be employed to monitor and develop robust protection against influenza B morbidity and mortality. Overall, we show that long-term diversification and infrequent selective sweeps, coupled with the reemergence of hemagglutinin deletion variants and antigenic drift of neuraminidase, are factors that contributed to successful circulation of diverse influenza B clades. Further divergence of hemagglutinin variants with poor cross-reactivity could potentially lead to circulation of 3 or more distinct influenza B viruses, further complicating influenza vaccine formulation and highlighting the urgent need for universal influenza vaccines.

phylogeny – genetic diversity – natural selection – antigenic – vaccine

Keywords: Seasonal Influenza; Influenza B; Evolution; Vaccines.

——

#Influenza B viruses from different #genetic backgrounds are variably impaired by #neuraminidase #inhibitor resistance-associated substitutions (Antiviral Res., abstract)

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

Antiviral Res. 2019 Nov 29:104669. doi: 10.1016/j.antiviral.2019.104669. [Epub ahead of print]

Influenza B viruses from different genetic backgrounds are variably impaired by neuraminidase inhibitor resistance-associated substitutions.

Pascua PNQ1, Marathe BM1, Bisen S1, Webby RJ1, Govorkova EA2.

Author information: 1 Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN, USA. 2 Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN, USA. Electronic address: elena.govorkova@stjude.org.

 

Abstract

Identifying evolutionary routes to antiviral resistance among influenza viruses informs molecular-based resistance surveillance and clinical decisions. To improve antiviral management and understand whether clinically identified neuraminidase (NA) inhibitor (NAI) resistance-associated markers affect influenza B viruses of the Victoria- or Yamagata-lineages differentially, we generated a panel of NAI-resistant viruses (carrying E105K, G145E, R150K, D197N, I221 L/N/T/V, H273Y, N294S, or G407S substitutions; B numbering) in B/Brisbane/60/2008 (BR/08) and B/Phuket/3073/2013 (PH/13). In both backgrounds, I221 L/N/T/V resulted in reduced or highly reduced inhibition (HRI) by one to three currently available NAIs. D197N reduced inhibition by all NAIs in BR/08 but only by oseltamivir and peramivir in PH/13; R150K caused HRI by all NAIs in PH/13. Although PH/13 generally retained or enhanced NA activity in the presence of the substitutions, enzymatic activity in BR/08 was detrimentally affected. Similarly, substrate affinity and catalysis were relatively stable in PH/13, but not in the BR/08 variants. E105K, R150K, and D197N attenuated replication efficiency of BR/08 in vitro and in mice; only E105K had this effect in PH/13. Notably, the I221 L/N/T/V substitutions did not severely impair replication, particularly in PH/13. Overall, our data show differential effects of NA substitutions in representative Victoria- and Yamagata-lineage viruses, suggesting distinct evolution of these viruses caused variable fitness and NAI susceptibility profiles when similar key NA substitutions arise. Because the viruses harboring the I221 NA substitutions displayed undiminished fitness and are commonly reported, this position is likely to be the most clinically relevant marker for NAI resistance among contemporary influenza B viruses.

Copyright © 2019. Published by Elsevier B.V.

KEYWORDS: Antiviral; Influenza B virus; Neuraminidase inhibitors; Resistance; Victoria-lineage; Yamagata-lineage

PMID: 31790712 DOI: 10.1016/j.antiviral.2019.104669

Keywords: Antivirals; Drugs Resistance; Influenza B; Oseltamivir.

——

Expression of 9-O- and 7,9-O-Acetyl Modified #Sialic Acid in Cells and Their Effects on #Influenza Viruses (MBio, abstract)

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

Expression of 9-O- and 7,9-O-Acetyl Modified Sialic Acid in Cells and Their Effects on Influenza Viruses

Karen N. Barnard, Brian R. Wasik, Justin R. LaClair, David W. Buchholz, Wendy S. Weichert, Brynn K. Alford-Lawrence, Hector C. Aguilar, Colin R. Parrish

Xiang-Jin Meng, Editor

DOI: 10.1128/mBio.02490-19

 

ABSTRACT

Sialic acids (Sia) are widely displayed on the surfaces of cells and tissues. Sia come in a variety of chemically modified forms, including those with acetyl modifications at the C-7, C-8, and C-9 positions. Here, we analyzed the distribution and amounts of these acetyl modifications in different human and canine cells. Since Sia or their variant forms are receptors for influenza A, B, C, and D viruses, we examined the effects of these modifications on virus infections. We confirmed that 9-O-acetyl and 7,9-O-acetyl modified Sia are widely but variably expressed across cell lines from both humans and canines. Although they were expressed on the cell surfaces of canine MDCK cell lines, they were located primarily within the Golgi compartment of human HEK-293 and A549 cells. The O-acetyl modified Sia were expressed at low levels of 1 to 2% of total Sia in these cell lines. We knocked out and overexpressed the sialate O-acetyltransferase gene (CasD1) and knocked out the sialate O-acetylesterase gene (SIAE) using CRISPR/Cas9 editing. Knocking out CasD1 removed 7,9-O- and 9-O-acetyl Sia expression, confirming previous reports. However, overexpression of CasD1 and knockout of SIAE gave only modest increases in 9-O-acetyl levels in cells and no change in 7,9-O-acetyl levels, indicating that there are complex regulations of these modifications. These modifications were essential for influenza C and D infection but had no obvious effect on influenza A and B infection.

 

IMPORTANCE

Sialic acids are key glycans that are involved in many different normal cellular functions, as well as being receptors for many pathogens. However, Sia come in diverse chemically modified forms. Here, we examined and manipulated the expression of 7,9-O- and 9-O-acetyl modified Sia on cells commonly used in influenza virus and other research by engineering the enzymes that produce or remove the acetyl groups.

Keywords: Influenza A; Influenza B; Influenza C; Influenza D; Viral pathogenesis.

——

#Influenza-like illness #outbreaks in #China during 2017-2018 surveillance season (Zhonghua Yu Fang Yi Xue Za Zhi, abstract)

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

Zhonghua Yu Fang Yi Xue Za Zhi. 2019 Oct 6;53(10):982-986. doi: 10.3760/cma.j.issn.0253-9624.2019.10.006.

[Influenza-like illness outbreaks in China during 2017-2018 surveillance season].

[Article in Chinese; Abstract available in Chinese from the publisher]

Liu LJ1, Yang J, Zhu F, Wang LJ, Guo Q, Tang J, Fang QQ, Wang DY, Chen T.

Author information: 1 Chinese National Influenza Center, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Key Laboratory for Medical Virology, National Health, Beijing 102206, China.

 

Abstract in English, Chinese

Objective:

To analyze epidemiological characteristics of influenza-like illness outbreaks in mainland China during 2017-2018 surveillance season, and to provide scientific evidence for developing influenza prevention and control strategies.

Methods:

We collected the data on reported influenza outbreaks in 2017-2018 surveillance season from China Influenza Surveillance Information System and China Public Health Emergency Management Information System and analyzed the data of laboratory-confirmed influenza-like illness outbreaks by descriptive epidemiological methods.

Results:

During the surveillance season, a total of 2 398 influenza-like illness outbreaks (with 10 or more incidences in an outbreak) in mainland China were reported, involving 87 084 patients, of which 2 323 were influenza outbreaks, involving 85 531 patients. The reported influenza-like illness outbreaks occurred most frequently from November 2017 to January 2018 in both the southern and northern regions and the highest peaks were in December 2017. During the period 1 850 influenza-like illness outbreaks (77.15%) were reported in the southern region, and 548 influenza-like illness outbreaks (22.85%) were reported in the northern region. The most of the outbreaks occurred in primary, secondary schools and nursery care schools, with a total of 2 210 reports (92.16%). And the majority of the outbreaks involved 10-29 incident cases. The dominant isolated virus strains for the outbreaks were influenza B (1 505 outbreaks, 62.76% of all the outbreaks).

Conclusion:

Seasonality of influenza outbreaks were observed in mainland China during 2017-2018 surveillance season and the reported influenza outbreaks were most frequently occurred in autumn-winter season and in southern China. Primary, secondary schools and nursery care schools are high-risk places for outbreaks, and the dominant isolated virus strains for the outbreaks were influenza B.

KEYWORDS: Disease attributes; Influenza, human; Pandemics

PMID: 31607042 DOI: 10.3760/cma.j.issn.0253-9624.2019.10.006

Keywords: Seasonal Influenza; Influenza B; Institutional outbreaks; China.

——-

#Hemagglutinin cleavability, acid-stability and #temperature dependence optimize #influenza B virus for #replication in human #airways (J Virol., abstract)

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

Hemagglutinin cleavability, acid-stability and temperature dependence optimize influenza B virus for replication in human airways

Manon Laporte, Annelies Stevaert, Valerie Raeymaekers, Talitha Boogaerts, Inga Nehlmeier, Winston Chiu, Mohammed Benkheil, Bart Vanaudenaerde, Stefan Pöhlmann, Lieve Naesens

DOI: 10.1128/JVI.01430-19

 

ABSTRACT

Influenza A virus (IAV) and influenza B virus (IBV) cause yearly epidemics with significant morbidity and mortality. When zoonotic IAVs enter the human population, the viral hemagglutinin (HA) requires adaptation to achieve sustained virus transmission. In contrast, IBV has been circulating in humans, its only host, for a long period of time. Whether this entailed adaptation of IBV HA to the human airways is unknown. To address this question, we compared two seasonal IAV (A/H1N1 and A/H3N2) and two IBV viruses (B/Victoria and B/Yamagata lineage) with regard to host-dependent activity of HA as the mediator of membrane fusion during viral entry. We first investigated proteolytic activation of HA, by covering all type II transmembrane serine protease (TTSP) and kallikrein enzymes, many of which proved present in human respiratory epithelium. Compared to IAV, the IBV HA0 precursor is cleaved by a broader panel of TTSPs and activated with much higher efficiency. Accordingly, knockdown of a single protease, TMPRSS2, abrogated spread of IAV but not IBV in human respiratory epithelial cells. Second, the HA fusion pH proved similar for IBV and human-adapted IAVs (one exception being HA of 1918 IAV). Third, IBV HA exhibited higher expression at 33°C, a temperature required for membrane fusion by B/Victoria HA. This indicates pronounced adaptation of IBV HA to the mildly acidic pH and cooler temperature of human upper airways. These distinct and intrinsic features of IBV HA are compatible with extensive host-adaptation during prolonged circulation of this respiratory virus in the human population.

 

IMPORTANCE

Influenza epidemics are caused by influenza A (IAV) and influenza B (IBV) viruses. IBV causes substantial disease, however it is far less studied than IAV. While IAV originates from animal reservoirs, IBV circulates in humans only. Virus spread requires that the viral hemagglutinin (HA) is active and sufficiently stable in human airways. We here resolve how these mechanisms differ between IBV and IAV. Whereas human IAVs rely on one particular protease for HA activation, this is not the case for IBV. Superior activation of IBV by several proteases should enhance shedding of infectious particles. IBV HA exhibits acid-stability and a preference for 33°C, indicating pronounced adaptation to the human upper airways, where the pH is mildly acidic and a cooler temperature exists. These adaptive features are rationalized by the long existence of IBV in humans, and may have broader relevance for understanding the biology and evolution of respiratory viruses.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Seasonal Influenza; Influenza B.

——