The CPSF30 Binding Site on the NS1A Protein of Influenza A Virus Is a Potential Antiviral Target

ABSTRACT The emergence of influenza A viruses resistant to the two existing classes of antiviral drugs highlights the need for additional antiviral drugs, particularly considering the potential threat of a pandemic of H5N1 influenza A viruses. Here, we determine whether influenza A virus replication can be selectively inhibited by blocking the ability of its NS1A protein to inhibit the 3′-end processing of cellular pre-mRNAs, including beta interferon (IFN-β) pre-mRNA. Pre-mRNA processing is inhibited via the binding of the NS1A protein to the cellular CPSF30 protein, and mutational inactivation of this NS1A binding site causes severe attenuation of the virus. We demonstrate that binding of CPSF30 is mediated by two of its zinc fingers, F2F3, and that the CPSF30/F2F3 binding site on the NS1A protein extends from amino acid 144 to amino acid 186. We generated MDCK cells that constitutively express epitope-tagged F2F3 in the nucleus, although at only approximately one-eighth the level of the NS1A protein produced during virus infection. Influenza A virus replication was inhibited in this cell line, whereas no inhibition was observed with influenza B virus, whose NS1B protein lacks a binding site for CPSF30. Influenza A virus, but not influenza B virus, induced increased production of IFN-β mRNA in the F2F3-expressing cells. These results, which indicate that F2F3 inhibits influenza A virus replication by blocking the binding of endogenous CPSF30 to the NS1A protein, point to this NS1A binding site as a potential target for the development of antivirals directed against influenza A virus.

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Influenza B viruses exhibit lower within-host diversity than influenza A viruses in human hosts

10.1101/791038 ◽

2019 ◽

Cited By ~ 4

Author(s):

Andrew L. Valesano ◽

William J. Fitzsimmons ◽

John T. McCrone ◽

Joshua G. Petrie ◽

Arnold S. Monto ◽

...

Keyword(s):

Genetic Diversity ◽

Influenza A Virus ◽

Influenza A ◽

Evolutionary Dynamics ◽

Influenza Viruses ◽

Influenza B Virus ◽

Influenza B ◽

Influenza A Viruses ◽

Community Based ◽

B Virus

AbstractInfluenza B virus undergoes seasonal antigenic drift more slowly than influenza A, but the reasons for this difference are unclear. While the evolutionary dynamics of influenza viruses play out globally, they are fundamentally driven by mutation, reassortment, drift, and selection within individual hosts. These processes have recently been described for influenza A virus, but little is known about the evolutionary dynamics of influenza B virus (IBV) at the level of individual infections and transmission events. Here we define the within-host evolutionary dynamics of influenza B virus by sequencing virus populations from naturally-infected individuals enrolled in a prospective, community-based cohort over 8176 person-seasons of observation. Through analysis of high depth-of-coverage sequencing data from samples from 91 individuals with influenza B, we find that influenza B virus accumulates lower genetic diversity than previously observed for influenza A virus during acute infections. Consistent with studies of influenza A viruses, the within-host evolution of influenza B viruses is characterized by purifying selection and the general absence of widespread positive selection of within-host variants. Analysis of shared genetic diversity across 15 sequence-validated transmission pairs suggests that IBV experiences a tight transmission bottleneck similar to that of influenza A virus. These patterns of local-scale evolution are consistent with influenza B virus’ slower global evolutionary rate.ImportanceThe evolution of influenza virus is a significant public health problem and necessitates the annual evaluation of influenza vaccine formulation to keep pace with viral escape from herd immunity. Influenza B virus is a serious health concern for children, in particular, yet remains understudied compared to influenza A virus. Influenza B virus evolves more slowly than influenza A, but the factors underlying this are not completely understood. We studied how the within-host diversity of influenza B virus relates to its global evolution by sequencing viruses from a community-based cohort. We found that influenza B virus populations have lower within-host genetic diversity than influenza A virus and experience a tight genetic bottleneck during transmission. Our work provides insights into the varying dynamics of influenza viruses in human infection.

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Inhibition of influenza A virus replication by influenza B virus nucleoprotein: An insight into interference between influenza A and B viruses

Virology ◽

10.1016/j.virol.2012.06.016 ◽

2012 ◽

Vol 432 (1) ◽

pp. 194-203 ◽

Cited By ~ 18

Author(s):

Asawin Wanitchang ◽

Jaraspim Narkpuk ◽

Peera Jaru-ampornpan ◽

Juggagarn Jengarn ◽

Anan Jongkaewwattana

Keyword(s):

Influenza A Virus ◽

Virus Replication ◽

Influenza A ◽

Influenza B Virus ◽

Influenza B ◽

B Virus ◽

Insight Into

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Molecular Characterization of Influenza A Viruses Detected in Children Attending Yangon Children’s Hospital, 2016

Myanmar Health Sciences Research Journal ◽

10.34299/mhsrj.00925 ◽

2019 ◽

Vol 31 (1) ◽

pp. 72-80

Keyword(s):

Phylogenetic Analysis ◽

Influenza A Virus ◽

Influenza A ◽

Epidemiological Studies ◽

Influenza Viruses ◽

Influenza B Virus ◽

Influenza B ◽

Influenza A Viruses ◽

B Virus ◽

Na Gene

Sequence analysis of the influenza virus strains is important for molecular epidemiological studies and evolutional studies of influenza viruses as well as for the assessment of vaccine effectiveness. The aim of this study was to determine and characterize predominant subtype of influenza A viruses among children attending Yangon Children’s Hospital (YCH). It was a cross-sectional descriptive study conducted at YCH. Nasopharyngeal swabs were collected from 153 children who attended the hospital due to influenza-like illness (ILI) during January-December, 2016. Viral RNA was extracted by QIAamp® Viral Mini Kit. Matrix genes of influenza A and influenza B virus were detected by multiplex Reverse TranscriptionPolymerase Chain Reaction (RT-PCR). Influenza A virus matrix gene positive samples were subjected to subtyping. Predominant subtypes were subjected to sequencing and phylogenetic analysis of their HA gene and neuraminidase (NA) gene. Influenza viruses were detected in about 14% of children with ILI. Among them, 55% showed influenza A virus positive and 45% showed influenza B virus positive. Influenza A (H3N2) virus was found to be predominant among influenza A virus positive children accounting for 83.4%. There was one case (8.3%) of influenza A (H1N1) pdm09 virus and one case (8.3%) of unsubtyped influenza A virus. Phylogenetic analysis of HA and NA gene of two Myanmar strains of H3N2 subtype revealed that they belonged to clade 3C.2a1. They had 99.3-99.4% nucleotide identity with A/Hong Kong/ 4801/2014, vaccine strain of H3N2 subtype, that was contained in southern hemisphere influenza vaccine for 2016 and northern hemisphere vaccine for 2016-2017 season. This study generated information useful for the assessment of influenza outbreaks, selection of upcoming vaccine strains and further evolutionary and epidemiological studies on influenza viruses.

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Influenza B virus M2 protein can functionally replace its influenza A virus counterpart in promoting virus replication

Virology ◽

10.1016/j.virol.2016.08.016 ◽

2016 ◽

Vol 498 ◽

pp. 99-108 ◽

Cited By ~ 3

Author(s):

Asawin Wanitchang ◽

Phonphimon Wongthida ◽

Anan Jongkaewwattana

Keyword(s):

Influenza A Virus ◽

Virus Replication ◽

Influenza A ◽

Influenza B Virus ◽

Influenza B ◽

M2 Protein ◽

B Virus

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Influenza B Viruses Exhibit Lower Within-Host Diversity than Influenza A Viruses in Human Hosts

Journal of Virology ◽

10.1128/jvi.01710-19 ◽

2019 ◽

Vol 94 (5) ◽

Cited By ~ 10

Author(s):

Andrew L. Valesano ◽

William J. Fitzsimmons ◽

John T. McCrone ◽

Joshua G. Petrie ◽

Arnold S. Monto ◽

...

Keyword(s):

Genetic Diversity ◽

Influenza A Virus ◽

Influenza A ◽

Evolutionary Dynamics ◽

Influenza Viruses ◽

Influenza B Virus ◽

Influenza B ◽

Influenza A Viruses ◽

Community Based ◽

B Virus

ABSTRACT Influenza B virus (IBV) undergoes seasonal antigenic drift more slowly than influenza A virus, but the reasons for this difference are unclear. While the evolutionary dynamics of influenza viruses play out globally, they are fundamentally driven by mutation, reassortment, drift, and selection at the level of individual hosts. These processes have recently been described for influenza A virus, but little is known about the evolutionary dynamics of IBV during individual infections and transmission events. Here, we define the within-host evolutionary dynamics of IBV by sequencing virus populations from naturally infected individuals enrolled in a prospective, community-based cohort over 8,176 person-seasons of observation. Through analysis of high depth-of-coverage sequencing data from samples from 91 individuals with influenza B, we find that IBV accumulates lower genetic diversity than previously observed for influenza A virus during acute infections. Consistent with studies of influenza A viruses, the within-host evolution of IBVs is characterized by purifying selection and the general absence of widespread positive selection of within-host variants. Analysis of shared genetic diversity across 15 sequence-validated transmission pairs suggests that IBV experiences a tight transmission bottleneck similar to that of influenza A virus. These patterns of local-scale evolution are consistent with the lower global evolutionary rate of IBV. IMPORTANCE The evolution of influenza virus is a significant public health problem and necessitates the annual evaluation of influenza vaccine formulation to keep pace with viral escape from herd immunity. Influenza B virus is a serious health concern for children, in particular, yet remains understudied compared to influenza A virus. Influenza B virus evolves more slowly than influenza A virus, but the factors underlying this are not completely understood. We studied how the within-host diversity of influenza B virus relates to its global evolution by sequencing viruses from a community-based cohort. We found that influenza B virus populations have lower within-host genetic diversity than influenza A virus and experience a tight genetic bottleneck during transmission. Our work provides insights into the varying dynamics of influenza viruses in human infection.

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Clinical Investigations. Comparison of Directigen Flu A+B with Real Time PCR in the Diagnosis of Influenza / Сравнение Иммунохроматографического Метода (Directigen Flu A+B) И Теста RT-PCR При Инфекциях Гриппа

Folia Medica ◽

10.1515/folmed-2015-0027 ◽

2015 ◽

Vol 57 (2) ◽

pp. 104-110 ◽

Cited By ~ 4

Author(s):

Golubinka Bosevska ◽

Nikola Panovski ◽

Elizabeta Janceska ◽

Vladimir Mikik ◽

Irena Kondova Topuzovska ◽

...

Keyword(s):

Real Time ◽

Influenza A Virus ◽

Real Time Pcr ◽

Influenza A ◽

Age Groups ◽

Influenza Viruses ◽

Influenza B Virus ◽

Influenza B ◽

B Virus ◽

Nose And Throat

AbstractEarly diagnosis and treatment of patients with influenza is the reason why physicians need rapid high-sensitivity influenza diagnostic tests that require no complex lab equipment and can be performed and interpreted within 15 min. The Aim of this study was to compare the rapid Directigen Flu A+B test with real time PCR for detection of influenza viruses in the Republic of Macedonia. MATERIALS AND METHODS: One-hundred-eight respiratory samples (combined nose and throat swabs) were routinely collected for detection of influenza virus during influenza seasons. Forty-one patients were pediatric cases and 59 were adult. Their mean age was 23 years. The patients were allocated into 6 age groups: 0 - 4 yrs, 5 - 9 yrs, 10 - 14 yrs, 15 - 19 yrs, 20-64 yrs and > 65 yrs. Each sample was tested with Directigen Flu A+B and CDC real time PCR kit for detection and typisation/subtypisation of influenza according to the lab diagnostic protocol. RESULTS: Directigen Flu A+B identified influenza A virus in 20 (18.5%) samples and influenza B virus in two 2 (1.9%) samples. The high specificity (100%) and PPV of Directigen Flu A+B we found in our study shows that the positive results do not need to be confirmed. The overall sensitivity of Directigen Flu A+B is 35.1% for influenza A virus and 33.0% for influenza B virus. The sensitivity for influenza A is higher among children hospitalized (45.0%) and outpatients (40.0%) versus adults. CONCLUSION: Directigen Flu A+B has relatively low sensitivity for detection of influenza viruses in combined nose and throat swabs. Negative results must be confirmed.

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Influenza A and B viruses in the population of Vojvodina, Serbia

Archives of Biological Sciences ◽

10.2298/abs1401043r ◽

2014 ◽

Vol 66 (1) ◽

pp. 43-50 ◽

Cited By ~ 2

Author(s):

J. Radovanov ◽

V. Milosevic ◽

I. Hrnjakovic ◽

V. Petrovic ◽

M. Ristic ◽

...

Keyword(s):

Influenza A ◽

Respiratory Infections ◽

Influenza Viruses ◽

Influenza B Virus ◽

Nasopharyngeal Swab ◽

Influenza B ◽

Influenza A Viruses ◽

B Virus ◽

Life Threatening ◽

Seasonal Epidemic

At present, two influenza A viruses, H1N1pdm09 and H3N2, along with influenza B virus co-circulate in the human population, causing endemic and seasonal epidemic acute febrile respiratory infections, sometimes with life-threatening complications. Detection of influenza viruses in nasopharyngeal swab samples was done by real-time RT-PCR. There were 60.2% (53/88) positive samples in 2010/11, 63.4% (52/82) in 2011/12, and 49.9% (184/369) in 2012/13. Among the positive patients, influenza A viruses were predominant during the first two seasons, while influenza B type was more active during 2012/13. Subtyping of influenza A positive samples revealed the presence of A (H1N1)pdm09 in 2010/11, A (H3N2) in 2011/12, while in 2012/13, both subtypes were detected. The highest seroprevalence against influenza A was in the age-group 30-64, and against influenza B in adults aged 30-64 and >65.

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Epidemiological and virological assessment of influenza activity in Europe during the winter 2005-2006

Eurosurveillance ◽

10.2807/esm.12.09.00733-en ◽

2007 ◽

Vol 12 (9) ◽

pp. 11-12 ◽

Cited By ~ 15

Author(s):

A Meijer ◽

T J Meerhoff ◽

L. E. Meuwissen ◽

J Van Der Velden ◽

W J Paget ◽

...

Keyword(s):

Influenza A ◽

New Caledonia ◽

Influenza B Virus ◽

Random Pattern ◽

Clinical Activity ◽

Influenza B ◽

Influenza A Viruses ◽

B Virus ◽

Influenza Activity ◽

Spread Pattern

Influenza activity in Europe during the winter 2005-2006 started late January - early February 2006 and first occurred in the Netherlands, France, Greece and England. Subsequently, countries were affected in a random pattern across Europe and the period of influenza activity lasted till the end of April. In contrast to the winter seasons in the period 2001-2005, no west-east pattern was detected. In 12 out of 23 countries, the consultation rates for influenza-like illness or acute respiratory infection in the winter 2005-2006 were similar or higher than in the winter 2004-2005, despite a dominance of influenza B viruses that normally cause milder disease than influenza A viruses. In the remaining 11 countries the consultation rates were lower to much lower than in the winter 2004-2005. The highest consultation rates were usually observed among children aged 0-14. The circulating influenza virus types and subtypes were distributed heterogeneously across Europe. Although the figures for total virus detections in Europe indicated a predominance of influenza B virus (58% of all virus detections), in many countries influenza B virus was predominant only early in the winter, whilst later there was a marked increase in influenza A virus detections. Among the countries where influenza A viruses were co-dominant with B viruses (9/29) or were predominant (4/29), the dominant influenza A subtype was H3 in seven countries and H1 in four countries. The vast majority of characterised influenza B viruses (90%) were similar to the B/Victoria/2/87 lineage of influenza B viruses that re-emerged in Europe in the winter 2004-2005 but were not included in the vaccine for the influenza season 2005-2006. This might help to explain the dominance of influenza B viruses in many countries in Europe during the winter 2005-2006. The influenza A(H3) and A(H1) viruses were similar to the reference strains included in the 2005-2006 vaccine, A/California/7/2004 (H3N2) and A/New Caledonia/20/99 (H1N1), respectively. In conclusion, the 2005-2006 influenza epidemic in Europe was characterised by moderate clinical activity, a heterogeneous spread pattern across Europe, and a variable virus dominance by country, although an overall dominance of influenza B viruses that did not match the virus strain included in the vaccine was observed.

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The importance of distinguishing COVID-19 from more common respiratory illnesses

Epidemiology and Infection ◽

10.1017/s0950268820001971 ◽

2020 ◽

Vol 148 ◽

Author(s):

Wei Zhao ◽

Xingzhi Xie ◽

Jun Liu

Keyword(s):

Computed Tomography ◽

Influenza A ◽

Influenza B Virus ◽

Influenza B ◽

Imaging Findings ◽

Influenza A Viruses ◽

Respiratory Illnesses ◽

B Virus ◽

Virus Pneumonia

Abstract We recruited 1591 patients who presented to our fever clinics from 23 January 2020 to 16 February 2020. The different imaging findings between COVID-19 pneumonia and influenza A viruses, influenza B virus pneumonia were also investigated. Most patients were infected by influenza A and B viruses in the flu-season. A laboratory kit is urgently needed to test different viruses simultaneously. Computed tomography can help early screen suspected patients with COVID-19 and differentiate different virus-related pneumonia.

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