Influenza B virus

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Influenza B virus
Ijms-18-00020-g001.B.png
Virion structure of influenza B virus
Virus classification OOjs UI icon edit-ltr.svg
(unranked): Virus
Realm: Riboviria
Kingdom: Orthornavirae
Phylum: Negarnaviricota
Class: Insthoviricetes
Order: Articulavirales
Family: Orthomyxoviridae
Genus: Betainfluenzavirus
Species:
Influenza B virus
Synonyms
Species
  • Influenza type B virus [1]
  • Influenza virus B [2]
Genus
  • Influenzavirus B [3]

Influenza B virus is the only species in the genus Betainfluenzavirus in the virus family Orthomyxoviridae .

Contents

Influenza B virus is only known to infect certain mammal species, including humans, ferrets, pigs, and seals. [4] [5] This limited host range is apparently responsible for the lack of influenza pandemics associated with influenza B virus, in contrast with those caused by the morphologically similar influenza A virus, as both mutate by both antigenic drift and reassortment. [6] [7] [8] Nevertheless, it is accepted that influenza B virus could cause significant morbidity and mortality worldwide, and significantly impacts adolescents and schoolchildren. [9]

There are two known circulating lineages of influenza B virus based on the antigenic properties of the surface glycoprotein hemagglutinin. The lineages are termed B/Yamagata/16/88-like and B/Victoria/2/87-like viruses. [10] The quadrivalent influenza vaccine licensed by the CDC has been designed to protect against both co-circulating lineages and as of 2016 has been shown to have greater effectiveness in prevention of influenza caused by influenza B virus than the previous trivalent vaccine. [11]

However, the B/Yamagata lineage might have become extinct in 2020/2021 due to COVID-19 pandemic measures. [12] In October 2023, the World Health Organization concluded that protection against the Yamagata lineage was no longer necessary in the seasonal flu vaccine, reducing the number of lineages targeted by the vaccine from four to three. [13] [14] For the 2024–2025 Northern Hemisphere influenza season, the US Food and Drug Administration (FDA) recommends removing B/Yamagata from all influenza vaccines. [15] The European Medicines Agency (EMA) recommends removing B/Yamagata from influenza vaccines for the 2024–2025 seasonal flu vaccine composition. [16]

Morphology

The influenza B virus capsid is enveloped while its virion consists of an envelope, a matrix protein, a nucleoprotein complex, a nucleocapsid, and a polymerase complex. It is sometimes spherical and sometimes filamentous. Its 500 or so surface projections are made of hemagglutinin and neuraminidase. [17]

Genome structure and genetics

The influenza B virus genome is 14,548 nucleotides long and consists of eight segments of linear negative-sense, single-stranded RNA. The multipartite genome is encapsidated, each segment in a separate nucleocapsid, and the nucleocapsids are surrounded by one envelope. [17]

The ancestor of influenza viruses A and B and the ancestor of influenza virus C are estimated to have diverged from a common ancestor around 8,000 years ago. Influenza viruses A and B are estimated to have diverged from a single ancestor around 4,000 years ago, while the subtypes of influenza A virus are estimated to have diverged 2,000 years ago. [18] Metatranscriptomics studies have also identified closely related "influenza B-like" viruses such as the Wuhan spiny eel influenza virus [19] and also "influenza B-like" viruses in a number of vertebrate species such as salamanders and fish. [20]

Diminishing the impact of this virus is the fact that, "in humans, influenza B viruses evolve slower than A viruses and faster than C viruses". [21] Influenza B virus mutates at a rate 2 to 3 times slower than type A. [22]

Vaccine

In 1936, Thomas Francis Jr. discovered the ferret influenza B virus. Also in 1936, Macfarlane Burnet made the discovery that influenza virus may be cultured in hen embryonated eggs. [23] This prompted research into the properties of the virus and the creation and application of inactivated vaccines in the late 1930s and early 1940s. Inactivated vaccines' usefulness as a preventative measure was proven in the 1950s. Later, 2003 saw the approval of the first live, attenuated influenza vaccine. [23] Looking into influenza B specifically, Thomas Francis Jr. isolated influenza B virus in 1936. However, it was not until 1940 that influenza B viruses were discovered. [24]

In 1942, a new bivalent vaccine was developed that protected against both the H1N1 strain of influenza A and the newly discovered influenza B virus. [25] In today's current world, even while some technology has advanced and flu vaccines now cover both strains of influenza A and B, the science is still based on findings from almost a century ago. [26] The viruses included in flu vaccines are changed each year to match the strains of flu that are most likely to make people sick that year since flu viruses can develop swiftly and new mutations have appeared each year, like H1N1. [26]

Even though there have been two different lineages of influenza B viruses that were circulating during most seasons, flu vaccinations were long meant to protect against three different flu viruses: the influenza A(H1N1), influenza A(H3N2), and one type of influenza B virus. [27] The second lineage of the B virus was since added to provide greater defense against circulating flu viruses. [27] Two influenza A viruses and two influenza B viruses have up until 2023 been among the four flu viruses that a quadrivalent vaccine was intended to protect against. As of 2022 all flu vaccines in the United States were quadrivalent. [27] The four main types of type A and B influenza viruses that are most likely to spread and make people sick during the upcoming flu season have been the targets of seasonal influenza (flu) vaccines. [27] All of the available flu vaccinations in the United States have offered protection against the influenza A(H1), A(H3), B/Yamagata, and B/Victoria lineage viruses. Each of these four vaccine virus components has been chosen based on which flu viruses are infecting people ahead of the upcoming flu season, how widely they are spreading, how well the vaccines from the previous flu season may protect against those flu viruses, and the vaccine viruses' capacity to offer cross-protection. [27]

For the 2022–2023 flu season, there were three flu vaccines that were preferentially recommended for people 65 years and older; various influenza (flu) vaccinations are authorized for use in people of various age groups. [27] In March 2022, the FDA's Vaccines and Related Biological Products Advisory Committee (VRBPAC) convened in Silver Spring, Maryland, to choose the influenza viruses that would make up the influenza vaccine for the 2022–2023 influenza season in the United States. The committee proposed using A(H1N1)pdm09, A(H3N2), and B/Austria/1359417/2021-like viruses for trivalent influenza vaccines to be utilized in the U.S. [28]

However, the B/Yamagata lineage might have become extinct in 2020/2021 due to COVID-19 pandemic measures, [12] and there have been no naturally occurring cases confirmed since March 2020. [13] [14] In October 2023, the World Health Organization concluded that protection against the Yamagata lineage was no longer necessary in the seasonal flu vaccine, reducing the number of lineages targeted by the vaccine from four to three. [13] [14]

Discovery and development

In 1940, an acute respiratory illness outbreak in Northern America led to the discovery of influenza B virus (IBV), which was later discovered to not have any antigenic cross-reactivity with influenza A virus (IAV). Based on calculations of the rate of amino acid substitutions in HA proteins, it was estimated that IBV and IAV diverged from one another around 4000 years ago. [4] However, the mechanisms of replication and transcription, as well as the functionality of the majority of viral proteins, appear to be largely conserved, with some unusual differences. [4] Although IBV has occasionally been found in seals and pigs, its primary host species is the human. [29] IBVs can also spread epidemics throughout the world, but they receive less attention than IAVs do due to their less prevalent nature, both in infecting hosts and in the symptoms that result from infection. IBVs used to be unclassified, but since the 1980s, they have been divided into the B/Yamagata and B/Victoria lineages. [30] IBVs have further divisions known as clades and sub-clades, just like IAVs do. [30]

Hemagglutinin (HA) and neuraminidase (NA) are two virus surface antigens that are constantly changing. [23] Antigenic drift or antigenic shift are two possible influenza viral changes. Small changes in the HA and NA of influenza viruses caused by antigenic drift result in the creation of novel strains that the immune system of humans might not be able to identify. [23] These emerging strains are the influenza virus's evolutionary responses to a potent immunological response across the population. The main cause of influenza recurrence is antigenic drift, which makes it essential to reevaluate and update the influenza vaccine's ingredient list every year. [23] Annual influenza outbreaks are caused by antigenic drift and declining immunity, when the residual defenses from prior exposures to related viruses are incomplete. Antigenic drift occurs in influenza A, B, and C. [23]

Hemagglutination inhibition experiments using ferret serum after infection allowed the identification of two very different antigenic influenza type B variants in the years 1988–1989. These viruses shared antigens with either B/Yamagata/16/88, a variation that was discovered in Japan in May 1988, or B/Victoria/2/87, the most recent reference strain. [31] The B/Victoria/2/87 virus shared antigens with all influenza B viruses discovered in the United States during an outbreak in the winter of 1988–1989. [31]

In Japan, influenza B virus reinfection was investigated virologically in 1985–1991 and epidemiologically in 1979–1991 in children. [32] Four influenza B virus outbreaks that each included antigenic drift occurred during the course of this study. Between the epidemics in 1987–1988 and 1989–1990, there was a significant genetic and antigenic change in the viruses. [32] Depending on the influenza seasons, the minimum rate of reinfection with influenza B virus for the entire period was between 2 and 25%. [32] Hemagglutination inhibition assays were used to examine the antigens of the influenza B virus primary and reinfection strains that were isolated from 18 children between the years of 1985 and 1990, which encompassed three epidemic periods. The findings revealed that reinfection occurred with the viruses recovered during the 1984–1985 and 1987–1988 influenza seasons, which belonged to the same lineage and were antigenically close. [32]

Today, the B/Yamagata lineage might be extinct as a result of COVID-19 pandemic measures, [12] and there have been no naturally occurring cases confirmed since March 2020. [13] [14] Although this development has resulted in updated recommendations regarding vaccine composition, [13] [14] continued surveillance is required to assess this conclusion fully, as pauses in IBV circulation have been observed before. [33]

Related Research Articles

<i>Influenza A virus</i> Species of virus

Influenza A virus (IAV) is a pathogen that causes the flu in birds and some mammals, including humans. It is an RNA virus whose subtypes have been isolated from wild birds. Occasionally, it is transmitted from wild to domestic birds, and this may cause severe disease, outbreaks, or human influenza pandemics.

<span class="mw-page-title-main">Antigenic shift</span> Process by which two or more different strains of a virus combine to form a new subtype

Antigenic shift is the process by which two or more different strains of a virus, or strains of two or more different viruses, combine to form a new subtype having a mixture of the surface antigens of the two or more original strains. The term is often applied specifically to influenza, as that is the best-known example, but the process is also known to occur with other viruses, such as visna virus in sheep. Antigenic shift is a specific case of reassortment or viral shift that confers a phenotypic change.

<span class="mw-page-title-main">Hemagglutinin (influenza)</span> Hemagglutinin of influenza virus

Influenza hemagglutinin (HA) or haemagglutinin[p] is a homotrimeric glycoprotein found on the surface of influenza viruses and is integral to its infectivity.

<i>Orthomyxoviridae</i> Family of RNA viruses including the influenza viruses

Orthomyxoviridae is a family of negative-sense RNA viruses. It includes seven genera: Alphainfluenzavirus, Betainfluenzavirus, Gammainfluenzavirus, Deltainfluenzavirus, Isavirus, Thogotovirus, and Quaranjavirus. The first four genera contain viruses that cause influenza in birds and mammals, including humans. Isaviruses infect salmon; the thogotoviruses are arboviruses, infecting vertebrates and invertebrates. The Quaranjaviruses are also arboviruses, infecting vertebrates (birds) and invertebrates (arthropods).

Antigenic drift is a kind of genetic variation in viruses, arising from the accumulation of mutations in the virus genes that code for virus-surface proteins that host antibodies recognize. This results in a new strain of virus particles that is not effectively inhibited by the antibodies that prevented infection by previous strains. This makes it easier for the changed virus to spread throughout a partially immune population. Antigenic drift occurs in both influenza A and influenza B viruses.

<span class="mw-page-title-main">Influenza vaccine</span> Vaccine against influenza

Influenza vaccines, colloquially known as flu shots, are vaccines that protect against infection by influenza viruses. New versions of the vaccines are developed twice a year, as the influenza virus rapidly changes. While their effectiveness varies from year to year, most provide modest to high protection against influenza. Vaccination against influenza began in the 1930s, with large-scale availability in the United States beginning in 1945.

<span class="mw-page-title-main">Live attenuated influenza vaccine</span> Nasal influenza vaccine

Live attenuated influenza vaccine (LAIV) is a type of influenza vaccine in the form of a nasal spray that is recommended for the prevention of influenza. It was developed by the Syrian-American epidemiologist Hunein Maassab.

<span class="mw-page-title-main">Swine influenza</span> Infection caused by influenza viruses endemic to pigs

Swine influenza is an infection caused by any of several types of swine influenza viruses. Swine influenza virus (SIV) or swine-origin influenza virus (S-OIV) refers to any strain of the influenza family of viruses that is endemic in pigs. As of 2009, identified SIV strains include influenza C and the subtypes of influenza A known as H1N1, H1N2, H2N1, H3N1, H3N2, and H2N3.

<span class="mw-page-title-main">Flu season</span> Recurring periods of influenza

Flu season is an annually recurring time period characterized by the prevalence of an outbreak of influenza (flu). The season occurs during the cold half of the year in each hemisphere. It takes approximately two days to show symptoms. Influenza activity can sometimes be predicted and even tracked geographically. While the beginning of major flu activity in each season varies by location, in any specific location these minor epidemics usually take about three weeks to reach its pinnacle, and another three weeks to significantly diminish.

<span class="mw-page-title-main">Influenza pandemic</span> Pandemic involving influenza

An influenza pandemic is an epidemic of an influenza virus that spreads across a large region and infects a large proportion of the population. There have been six major influenza epidemics in the last 140 years, with the 1918 flu pandemic being the most severe; this is estimated to have been responsible for the deaths of 50–100 million people. The 2009 swine flu pandemic resulted in under 300,000 deaths and is considered relatively mild. These pandemics occur irregularly.

<span class="mw-page-title-main">Influenza A virus subtype H3N2</span> Virus subtype

Influenza A virus subtype H3N2 (A/H3N2) is a subtype of viruses that causes influenza (flu). H3N2 viruses can infect birds and mammals. In birds, humans, and pigs, the virus has mutated into many strains. In years in which H3N2 is the predominant strain, there are more hospitalizations.

<span class="mw-page-title-main">Fujian flu</span> Strains of influenza

Fujian flu refers to flu caused by either a Fujian human flu strain of the H3N2 subtype of the Influenza A virus or a Fujian bird flu strain of the H5N1 subtype of the Influenza A virus. These strains are named after Fujian, a coastal province in Southeast China.

<span class="mw-page-title-main">Influenza</span> Infectious disease

Influenza, commonly known as "the flu" or just "flu", is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These symptoms begin from one to four days after exposure to the virus and last for about 2–8 days. Diarrhea and vomiting can occur, particularly in children. Influenza may progress to pneumonia, which can be caused by the virus or by a subsequent bacterial infection. Other complications of infection include acute respiratory distress syndrome, meningitis, encephalitis, and worsening of pre-existing health problems such as asthma and cardiovascular disease.

<span class="mw-page-title-main">Pandemic H1N1/09 virus</span> Virus responsible for the 2009 swine flu pandemic

The pandemic H1N1/09 virus is a swine origin influenza A virus subtype H1N1 strain that was responsible for the 2009 swine flu pandemic. This strain is often called swine flu by the public media. For other names, see the Nomenclature section below.

<span class="mw-page-title-main">Historical annual reformulations of the influenza vaccine</span>

Since 1999, the World Health Organization (WHO) has issued annual recommendations for influenza vaccine formulations. One reformulation of the influenza vaccine is for the Northern Hemisphere, and the other is for the Southern Hemisphere. Both recommendations are trivalent, i.e. featuring three strains.

Cell-based vaccines are developed from mammalian or more rarely avian or insect cell lines rather than the more common method which uses the cells in embryonic chicken eggs to develop the antigens. The potential use of cell culture techniques in developing viral vaccines has been widely investigated in the 2000s as a complementary and alternative platform to the current egg-based strategies.

<span class="mw-page-title-main">Universal flu vaccine</span> Vaccine that prevents infection from all strains of the flu

A universal flu vaccine is a flu vaccine that is effective against all influenza strains regardless of the virus sub type, antigenic drift or antigenic shift. Hence it should not require modification from year to year. As of 2021 no universal flu vaccine had been approved for general use, several were in development, and one was in clinical trial.

Type A influenza vaccine is for the prevention of infection of influenza A virus and also the influenza-related complications. Different monovalent type A influenza vaccines have been developed for different subtypes of influenza A virus including H1N1 and H5N1. Both intramuscular injection or intranasal spray are available on market. Unlike the seasonal influenza vaccines which are used annually, they are usually used during the outbreak of certain strand of subtypes of influenza A. Common adverse effects includes injection site reaction and local tenderness. Incidences of headache and myalgia were also reported with H1N1 whereas cases of fever has also been demonstrated with H5N1 vaccines. It is stated that immunosuppressant therapies would reduce the therapeutic effects of vaccines and that people with egg allergy should go for the egg-free preparations.

<span class="mw-page-title-main">Polyvalent influenza vaccine</span> Vaccine against multiple flu strains

Polyvalent influenza vaccine is a type of influenza vaccine that provides immunity against more than one type of antigen. In the second week after receiving the flu shot, the body's immune system is triggered by the antigens so the body starts producing antibodies. These antibodies help fight against influenza viruses. Influenza symptoms and deaths can be prevented by getting an influenza vaccine every year. Currently circulating influenza strains that can cause seasonal epidemics include influenza A viruses, which can be further divided into subtype A(H1N1) and A(H3N2), and influenza B viruses.

References

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