Influenza A and B Virus Intertypic Reassortment through Compatible Viral Packaging Signals

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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Haemagglutination-inhibition antibodies against influenza A and influenza B in maternal and neonatal sera

Journal of Hygiene ◽

10.1017/s0022172400053353 ◽

1978 ◽

Vol 80 (1) ◽

pp. 13-19 ◽

Cited By ~ 6

Author(s):

N. Masurel ◽

J. I. de Bruijne ◽

H. A. Beuningh ◽

H. J. A. Schouten

Keyword(s):

Influenza Virus ◽

Maternal Age ◽

Influenza A ◽

Haemagglutination Inhibition ◽

Influenza Viruses ◽

Influenza B Virus ◽

Influenza B ◽

B Virus ◽

Duration Of Pregnancy ◽

Pregnancy And Birth

SUMMARYHaemagglutination inhibition (HI) antibodies against the influenza viruses A/Hong Kong/8/68 (H3N2) and B/Nederland/77/66 were determined in 420 paired sera from mothers and newborns (umbilical cord sera), sampled in 1970–1.A higher concentration of antibodies against influenza A virus was found more frequently in neonatal than in maternal sera. By contrast, low titres against influenza B virus were more frequently observed in neonatal than in maternal sera. Maternal age, duration of pregnancy, and birth-weight did not affect the results of the tests.It is suggested that the titre of the newborn against an epidemic influenza virus can be predicted from that of the mother. Furthermore, the maternal titre may be an indication of the susceptibility of the newborn infant to influenza infections.

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A 2018/2019. évi légúti szezonban influenzaszerű betegséggel kórházban ellátott felnőtt betegek klinikai és mikrobiológiai jellemzése

Orvosi Hetilap ◽

10.1556/650.2020.32064 ◽

2020 ◽

Vol 161 (52) ◽

pp. 2179-2187

Author(s):

Boglárka Laky ◽

Bálint Gergely Szabó

Keyword(s):

Influenza A ◽

Primary Outcome ◽

Influenza Season ◽

Respiratory Viruses ◽

Complication Rates ◽

Icu Admission ◽

B Virus ◽

All Cause Mortality ◽

Significant Burden ◽

Observational Cohort

Összefoglaló. Bevezetés, célkitűzés: Az influenzaszezonban fellépő, elsősorban virális megbetegedések jelentős morbiditási és mortalitási teherrel rendelkeznek. Célunk volt az influenzaszerű betegséggel (ILI) és akut légúti betegséggel (ARI) kórházba felvett felnőtt betegek mikrobiológiai és klinikai karakterisztikájának leírása. Módszerek: Egycentrumos, obszervációs kohorszvizsgálatunk során a 2018/2019. évi légúti szezonban a Dél-pesti Centrumkórház – Országos Hematológiai és Infektológiai Intézet Infektológiai Osztályára ILI/ARI diagnózissal felvett betegek eseteit dolgoztuk fel a kórház elektronikus adatbázisának segítségével. Bevonásra azon betegek kerültek, akiknél légúti PCR-vizsgálat történt. A bevont betegeket alcsoportokra osztottuk: klinikai ILI/ARI, PCR-pozitív ILI/ARI influezavírussal, PCR-pozitív ILI/ARI más vírussal. Elsődleges kimenetelnek a komplikált betegséglefolyást, másodlagos kimenetelnek a kórházi összhalálozást, az intenzív osztályos (ICU-) felvételt, az osztályos ápolás hosszát (LOS) és az ICU LOS-t választottuk. Statisztikai összehasonlításra a Mann–Whitney-féle U-próbát, a Fisher-féle egzakt tesztet használtuk. Eredmények: A bevont 112 eset 42,8%-ában igazolódott influenza A- vagy B-vírus, 7,1%-ban egyéb légúti vírus, második leggyakrabban az RSV etiológiai szerepe. Megelőző kórházi ellátás szignifikánsan gyakrabban fordult elő PCR-pozitív ILI/ARI esetekben (23,2% vs. 42,8%; p = 0,04); ugyanezen betegek körében a panaszok kezdetétől a diagnózisig eltelt idő kb. 1 nappal rövidebb volt (3,0 ± 4,0 vs. 4,0 ± 5,0 nap; p = 0,02). A komplikációk gyakoriságát hasonló nagyságúnak találtuk (46,4% vs. 51,8%; p = 0,72), a leggyakoribb szövődmény a tüdőgyulladás volt (45,5%). ICU-felvételre az esetek 5,4%-ában volt szükség, a kórházi összhalálozás 3,6%-nak adódott. A medián LOS 8,5 ± 8,0 nap, a medián ICU LOS ideje 20,5 ± 30,5 nap volt. Következtetés: A vizsgált légúti szezonban ILI/ARI diagnózissal felvett betegek jelentős részében influenza-, kisebb hányadban egyéb légúti vírusok voltak felelősek a klinikumért. A leggyakoribb szövődmény a pneumonia volt. A légúti PCR-vizsgálat lehetőséget nyújthat az etiológia tisztázására. Orv Hetil. 2020; 161(52): 2179–2187. Summary. Introduction, objectives: A significant burden of morbidity and mortality is caused by seasonal outbreaks of respiratory viruses. Our aim was to identify clinical and microbiological differences among adult patients hospitalized with acute respiratory infection (ARI) or influenza-like illness (ILI). Methods: A single-center observational cohort study was conducted at South Pest Central Hospital, National Institute of Hematology and Infectious Diseases during the 2018/2019 influenza season. Patients were identified using the hospital database, and included in the study if respiratory PCR sampling was done during hospital stay. Subgroups were created according to the identified etiology: clinical ILI/ARI (no PCR positivity), PCR positive ILI/ARI with influenza, PCR positive ILI/ARI with other virus(es). Primary outcome was the occurrence of any complication, secondary outcomes were in-hospital all-cause mortality, intensive care unit (ICU) admission, length of stay (LOS) and ICU LOS. For statistical analysis, Mann–Whitney and Fisher’s tests were used. Results: From 112 identified cases, 42.8% were caused by influenza A or B, 7.1% by other viruses, notably RSV. PCR positivity frequently associated with prior hospitalization (23.2% vs. 42.8%; p = 0.04), and shorter time from symptom onset to diagnosis (3.0 ± 4.0 vs. 4.0 ±5.0 days, p = 0.02). Complication rates were similar among subgroups (46.4% vs. 51.8%; p = 0.72), with pneumonia as a leading complication (45.5%). ICU admission was necessary in 5.4%, in-hospital all-cause mortality was 3.6%. Median LOS and ICU LOS were 8.5 ± 8.0 and 20.5 ± 30.5 days, respectively. Conclusion: During the 2018/2019 season, most ILI/ARI cases were caused by influenza, but other respiratory viruses could also be detected in lower rates. Pneumonia was the most common complication. Respiratory PCR sampling might provide a feasible way of etiology identification. Orv Hetil. 2020; 161(52): 2179–2187.

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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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Codon conservation in the influenza A virus genome defines RNA packaging signals

Nucleic Acids Research ◽

10.1093/nar/gkm087 ◽

2007 ◽

Vol 35 (6) ◽

pp. 1897-1907 ◽

Cited By ~ 128

Author(s):

Julia R. Gog ◽

Emmanuel Dos Santos Afonso ◽

Rosa M. Dalton ◽

India Leclercq ◽

Laurence Tiley ◽

...

Keyword(s):

Influenza A Virus ◽

Influenza A ◽

Virus Genome ◽

Rna Packaging ◽

Packaging Signals

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Rewiring the RNAs of influenza virus to prevent reassortment

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.0908897106 ◽

2009 ◽

Vol 106 (37) ◽

pp. 15891-15896 ◽

Cited By ~ 52

Author(s):

Qinshan Gao ◽

Peter Palese

Keyword(s):

Influenza Virus ◽

Influenza A Virus ◽

Influenza A ◽

Nonstructural Protein ◽

Influenza Viruses ◽

Ha Gene ◽

Ns Gene ◽

Virus Rna ◽

Reassortant Viruses ◽

Packaging Signals

Influenza viruses contain segmented, negative-strand RNA genomes. Genome segmentation facilitates reassortment between different influenza virus strains infecting the same cell. This phenomenon results in the rapid exchange of RNA segments. In this study, we have developed a method to prevent the free reassortment of influenza A virus RNAs by rewiring their packaging signals. Specific packaging signals for individual influenza virus RNA segments are located in the 5′ and 3′ noncoding regions as well as in the terminal regions of the ORF of an RNA segment. By putting the nonstructural protein (NS)-specific packaging sequences onto the ORF of the hemagglutinin (HA) gene and mutating the packaging regions in the ORF of the HA, we created a chimeric HA segment with the packaging identity of an NS gene. By the same strategy, we made an NS gene with the packaging identity of an HA segment. This rewired virus had the packaging signals for all eight influenza virus RNAs, but it lost the ability to independently reassort its HA or NS gene. A similar approach can be applied to the other influenza A virus segments to diminish their ability to form reassortant viruses.

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Serum High-Mobility-Group Box 1 as a Biomarker and a Therapeutic Target during Respiratory Virus Infections

mBio ◽

10.1128/mbio.00246-18 ◽

2018 ◽

Vol 9 (2) ◽

Cited By ~ 16

Author(s):

Mira C. Patel ◽

Kari Ann Shirey ◽

Marina S. Boukhvalova ◽

Stefanie N. Vogel ◽

Jorge C. G. Blanco

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Influenza A ◽

Influenza Virus Infection ◽

High Mobility ◽

Influenza B Virus ◽

Influenza B ◽

Lung Pathology ◽

B Virus ◽

Cotton Rats

ABSTRACT Host-derived “danger-associated molecular patterns” (DAMPs) contribute to innate immune responses and serve as markers of disease progression and severity for inflammatory and infectious diseases. There is accumulating evidence that generation of DAMPs such as oxidized phospholipids and high-mobility-group box 1 (HMGB1) during influenza virus infection leads to acute lung injury (ALI). Treatment of influenza virus-infected mice and cotton rats with the Toll-like receptor 4 (TLR4) antagonist Eritoran blocked DAMP accumulation and ameliorated influenza virus-induced ALI. However, changes in systemic HMGB1 kinetics during the course of influenza virus infection in animal models and humans have yet to establish an association of HMGB1 release with influenza virus infection. To this end, we used the cotton rat model that is permissive to nonadapted strains of influenza A and B viruses, respiratory syncytial virus (RSV), and human rhinoviruses (HRVs). Serum HMGB1 levels were measured by an enzyme-linked immunosorbent assay (ELISA) prior to infection until day 14 or 18 post-infection. Infection with either influenza A or B virus resulted in a robust increase in serum HMGB1 levels that decreased by days 14 to 18. Inoculation with the live attenuated vaccine FluMist resulted in HMGB1 levels that were significantly lower than those with infection with live influenza viruses. RSV and HRVs showed profiles of serum HMGB1 induction that were consistent with their replication and degree of lung pathology in cotton rats. We further showed that therapeutic treatment with Eritoran of cotton rats infected with influenza B virus significantly blunted serum HMGB1 levels and improved lung pathology, without inhibiting virus replication. These findings support the use of drugs that block HMGB1 to combat influenza virus-induced ALI. IMPORTANCE Influenza virus is a common infectious agent causing serious seasonal epidemics, and there is urgent need to develop an alternative treatment modality for influenza virus infection. Recently, host-derived DAMPs, such as oxidized phospholipids and HMGB1, were shown to be generated during influenza virus infection and cause ALI. To establish a clear link between influenza virus infection and HMGB1 as a biomarker, we have systematically analyzed temporal patterns of serum HMGB1 release in cotton rats infected with nonadapted strains of influenza A and B viruses and compared these patterns with a live attenuated influenza vaccine and infection by other respiratory viruses. Towards development of a new therapeutic modality, we show herein that blocking serum HMGB1 levels by Eritoran improves lung pathology in influenza B virus-infected cotton rats. Our study is the first report of systemic HMGB1 as a potential biomarker of severity in respiratory virus infections and confirms that drugs that block virus-induced HMGB1 ameliorate ALI.

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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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