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



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.



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.


Susceptibility of #Influenza A, B, C, and D Viruses to #Baloxavir (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 25, Number 10—October 2019 / Dispatch

Susceptibility of Influenza A, B, C, and D Viruses to Baloxavir

Vasiliy P. Mishin, Mira C. Patel, Anton Chesnokov, Juan De La Cruz, Ha T. Nguyen, Lori Lollis, Erin Hodges, Yunho Jang, John Barnes, Timothy Uyeki, Charles T. Davis, David E. Wentworth, and Larisa V. Gubareva

Author affiliations: Centers for Disease Control and Prevention, Atlanta, Georgia, USA (V.P. Mishin, M.C. Patel, A. Chesnokov, J. De La Cruz, H.T. Nguyen, L. Lollis, E. Hodges, Y. Jang, J. Barnes, T. Uyeki, C.T. Davis, D.E. Wentworth, L.V. Gubareva); Battelle Memorial Institute, Atlanta (M.C. Patel, J. De La Cruz, H.T. Nguyen, L. Lollis)



Baloxavir showed broad-spectrum in vitro replication inhibition of 4 types of influenza viruses (90% effective concentration range 1.2–98.3 nmol/L); susceptibility pattern was influenza A ˃ B ˃ C ˃ D. This drug also inhibited influenza A viruses of avian and swine origin, including viruses that have pandemic potential and those resistant to neuraminidase inhibitors.

Keywords: Antivirals; Drugs Resistance; Oseltamivir; Favipiravir; Baloxavir; Influenza A; Influenza B; Influenza C; Influenza D; H1N1pdm09; H3N2; H7N9.


Identification of #Influenza C Virus in Young South #Korean #Children, from October 2013 to September 2016 (J Clin Virol., abstract)

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

Journal of Clinical Virology / Available online 27 March 2019 / In Press, Accepted Manuscript / Short communication

Identification of Influenza C Virus in Young South Korean Children, from October 2013 to September 2016

Han Sol Lee a,1, Sooyeon Lim a,b,1, Ji Yun Noh a, Joon Young Song a, Hee Jin Cheong a,c, Jung Hwa Lee d, Sung Il Woo e, Woo Joo Kim a,c

{a} Division of Infectious Diseases, Department of Internal Medicine, Korea University College of Medicine, Seoul, South Korea; {b} Division of Brain Korea 21 Program for Biomedicine Science, College of Medicine, Korea University, Seoul, South Korea; {c} Asia Pacific Influenza Institute, Korea University College of Medicine, Seoul, South Korea; {d} Department of Pediatrics, Korea University College of Medicine, Seoul, South Korea; {e} Department of Pediatrics, Chungbuk National University Hospital and College of Medicine, Cheongju, South Korea

Received 7 January 2019, Revised 8 March 2019, Accepted 26 March 2019, Available online 27 March 2019.




  • Five (1.22%) influenza C viruses were detected in 409 RV16 test negative samples during the influenza season.
  • Young children are infected with influenza C virus and are at risk for acute respiratory illness.
  • C/Sao Paulo/387/82-like lineage viruses circulated in South Korea.
  • Re-assortment event was observed in the C/Seoul/APD462/2015 strain.




Influenza C virus has been largely neglected, compared to influenza A orB viruses, and is not routinely tested in clinical practices. However, several studies have indicated that influenza C virus causes severe acute respiratory illness and pneumonia in all ages.


We conducted a study to identify influenza C virus among young children in South Korea.Study design. From October 2013 to September 2016, 973 young children with influenzalike illness (ILI) were enrolled at three university hospitals. We tested nasopharyngeal samples for 16 types of respiratory viruses. Among the tested samples, 564 were positive for one or more respiratory viruses. Except for the samples where 16 types of respiratory viruses were found, 409 negative samples were examined for the presence of influenza C virus, using a matrix gene specific primer set.


Among 409 nasopharyngeal samples, five influenza C viruses were detected. The manifestation of influenza C virus infection in young children was observed acute respiratory illness, such as fever, rhinorrhea, and cough, but no pneumonia or severe respiratory illness. Nucleotide sequencing was conducted and a phylogenetic tree was generated. We found that C/Sao Paulo/387/82-like lineage viruses circulated in South Korea, and the fully sequenced virus (C/Seoul/APD462/2015) was closely related to C/Victoria/2/2012 and C/Tokyo/4/2014 strains.


This study was the first report of influenza C virus detection in South Korea. Although severe illness was not observed in this study, we suggest the necessity for influenza C virus testing in pediatric patients with ILI, considering other reports of severe illnesses caused by influenza C virus infections.

Keywords: Influenza C virus – South Korea – Phylogenetic analysis

1 These authors contributed equally to this work.

© 2019 Published by Elsevier B.V.

Keywords: Seasonal Influenza; Influenza C; South Korea.


Emerging #Influenza D Virus #Threat: What We Know so Far! (J Clin Med., abstract)

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

J Clin Med. 2019 Feb 5;8(2). pii: E192. doi: 10.3390/jcm8020192.

Emerging Influenza D Virus Threat: What We Know so Far!

Asha K1, Kumar B2.

Author information: 1 Department of Microbiology and Immunology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA. 2 Department of Microbiology and Immunology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA.



Influenza viruses, since time immemorial, have been the major respiratory pathogen known to infect a wide variety of animals, birds and reptiles with established lineages. They belong to the family Orthomyxoviridae and cause acute respiratory illness often during local outbreaks or seasonal epidemics and occasionally during pandemics. Recent studies have identified a new genus within the Orthomyxoviridae family. This newly identified pathogen, D/swine/Oklahoma/1334/2011 (D/OK), first identified in pigs with influenza-like illness was classified as the influenza D virus (IDV) which is distantly related to the previously characterized human influenza C virus. Several other back-to-back studies soon suggested cattle as the natural reservoir and possible involvement of IDV in the bovine respiratory disease complex was established. Not much is known about its likelihood to cause disease in humans, but it definitely poses a potential threat as an emerging pathogen in cattle-workers. Here, we review the evolution, epidemiology, virology and pathobiology of influenza D virus and the possibility of transmission among various hosts and potential to cause human disease.

KEYWORDS: emerging pathogen; epidemic; influenza; influenza A virus (IAV); influenza B virus (IBV); influenza C virus (ICV); influenza D virus (IDV); influenza-like illness; pandemic; respiratory illness

PMID: 30764577 DOI: 10.3390/jcm8020192

Keywords: Influenza C; Influenza D; Cattle; Pigs.


Detection of #Influenza C Virus #Infection among Hospitalized #Patients, #Cameroon (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 25, Number 3—March 2019 / Research Letter

Detection of Influenza C Virus Infection among Hospitalized Patients, Cameroon

Richard Njouom  , Gwladys Chavely Monamele, Burcu Ermetal, Serge Tchatchouang, Sylvie Moyo-Tetang, John W. McCauley, and Rodney S. Daniels

Author affiliations: Centre Pasteur du Cameroon, Yaounde, Cameroon (R. Njouom, G.C. Monamele, S. Tchatchouang); The Francis Crick Institute, London, United Kingdom (B. Ermetal, J.W. McCauley, R.S. Daniels); Centre Hospitalier d’Essos, Yaounde (S. Moyo-Tetang)



We report 3 cases of influenza C virus in children hospitalized with severe acute respiratory infection in Cameroon. Two of these case-patients had grave clinical manifestations, but all 3 recovered. The lack of specific antiviral drugs for influenza C virus highlights the need to identify and describe cases involving this virus.

Keywords: Influenza C; SARI; Cameroon.


Unique directional motility of #influenza C virus controlled by its filamentous #morphology and short-range motions (J Virol., abstract)

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

Unique directional motility of influenza C virus controlled by its filamentous morphology and short-range motions

Tatsuya Sakai a#,  Hiroaki Takagi b, Yasushi Muraki c and Mineki Saito a

Author Affiliations: Department of Microbiology, Kawasaki Medical School, Kurashiki, Okayama, Japan{a}; Department of Physics, School of Medicine, Nara Medical University, Kashihara, Nara, Japan{b}; Division of Infectious Diseases and Immunology, Department of Microbiology, School of Medicine, Iwate Medical University, Yahaba, Iwate, Japan{c}



Influenza virus motility is based on cooperation between two viral spike proteins, hemagglutinin (HA) and neuraminidase (NA), and is a major determinant of virus infectivity. To translocate a virus particle on the cell surface, HA molecules exchange viral receptors and NA molecules accelerate the receptor exchange of HA. This type of virus motility was recently identified in influenza A virus (IAV). To determine if other influenza virus types have a similar receptor-exchange mechanism-driven motility, we investigated influenza C virus (ICV) motility on a receptor-fixed glass surface. This system excludes receptor mobility, which makes it more optimal than a cell surface for demonstrating virus motility by receptor-exchange. Like IAV, ICV was observed to move across the receptor-fixed surface. However, in contrast with the random movement of IAV, a filamentous ICV strain, Ann Arbor/1/50 (AA), moved straight, in a directed manner, and at a constant rate, whereas a spherical ICV strain, Taylor/1233/47 (Taylor), moved randomly, similar to IAV. The AA and Taylor viruses each moved with a combination of gradual (crawling) and rapid (gliding) motions, but the lengths of crawling and gliding for the AA virus were shorter than those of the Taylor virus. Our findings indicate that, like IAV, ICV also has a motility that is driven by the receptor-exchange mechanism. However, compared with IAV movement, filamentous ICV movement is highly regulated in both direction and speed. Control of ICV movement is based on its specific motility employing short crawling and gliding motions as well as its own filamentous morphology.



Influenza virus enters into a host cell for infection via cellular endocytosis. Human influenza virus infects epithelial cells of the respiratory tract, the surfaces of which are hidden by abundant cilia that are inactive in endocytosis. An open question is the manner by which the virus migrates to endocytosis-active domains. In analyzing individual virus behaviors through single-virus tracking, we identified a novel function of the hemagglutinin and esterase of influenza C virus (ICV) as motility machinery. Hemagglutinin iteratively exchanges a viral receptor, causing virus movement. Esterase degrades the receptors along the trajectory traveled by the virus and prevents the virus from moving backward, causing directional movement. We propose that ICV has unique motile machinery directionally controlled via hemagglutinin sensing the receptor density manipulated by esterase.



#Address correspondence to Tatsuya Sakai,

Copyright © 2017 Sakai et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

Keywords: Influenza C.


Detection of #influenza C viruses among #outpatients and patients hospitalized for #SARI, #Minnesota, 2013-2016 (Clin Infect Dis., abstract)

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

Detection of influenza C viruses among outpatients and patients hospitalized for severe acute respiratory infection, Minnesota, 2013-2016

Beth K Thielen, MD, PhD Hannah Friedlander, MPH Sarah Bistodeau, BSBo Shu, PhD Brian Lynch Karen Martin, MPH Erica Bye, MPHKathyrn Como-Sabetti, MPH David Boxrud, MS Anna K Strain, PhDSandra S Chaves, MD, MSc Andrea Steffens, MPH Ashley L Fowlkes, MPHStephen Lindstrom, PhD Ruth Lynfield, MD

Clinical Infectious Diseases, cix931,

Published:  23 October 2017




Existing literature suggests that influenza C typically causes mild respiratory tract disease. However, clinical and epidemiological data are limited.


Four outpatient clinics and three hospitals submitted clinical data and respiratory specimens through a surveillance network for acute respiratory infection (ARI) during May 2013 through December 2016. Specimens were tested using multi-target nucleic acid amplification tests (NAAT) for 19-22 respiratory pathogens, including influenza C.


Influenza C virus was detected among 59 of 10,202 (0.58%) hospitalized SARI cases and 11 of 2,282 (0.48%) outpatients. Most detections occurred from December to March, with 73% during the 2014-2015 season. Influenza C detections occurred among patients of all ages, with similar rates between inpatients and outpatients. The highest rate of detection occurred among children aged 6 to 24 months (1.2%). Among hospitalized cases, seven required intensive care. Medical co-morbidities were reported in 58% of hospitalized cases and all who required intensive care. At least one other respiratory pathogen was detected in 40 (66%) cases, most commonly rhinovirus/enterovirus (25%) and respiratory syncytial virus (RSV) (20%). The hemagglutinin-esterase-fusion (HEF) gene was sequenced in 37 specimens, and both C/Kanagawa and C/Sao Paulo lineages were detected in inpatients and outpatients.


We found seasonal circulation of influenza C with year-to-year variability. Detection was most frequent among young children, but occurred in all ages. Some cases positive for influenza C, particularly those with co-morbid conditions, had severe disease, suggesting a need for further study of the role of influenza C virus in the pathogenesis of respiratory disease.

influenza virus, hospitalization, influenza-like illness, biosurveillance

Topic:  influenza – enterovirus – ambulatory care facilities – child – esterase – genes – hemagglutinin – inpatient – intensive care – outpatients – respiratory syncytial viruses – respiratory tract diseases – respiratory tract infections – rhinovirus – influenza c virus – morbidity – viruses – pathogenic organism – surveillance, medical – nucleic acid amplification tests

Issue Section:  Major Article

Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Keywords: Seasonal Influenza; Influenza C; USA.