Overview

H3N2v, more commonly known as Influenza A, is a virus that causes the (swine) flu (CDC). The flu is different from the common cold. Both the flu and the cold are caused by viruses, but are different types (strains) of viruses. Similarly, they both affect the respiratory system, and are also contagious. Unlike the common cold, however, the flu is likely to have harsher symptoms and can lead to additional complications (CDC). Despite this likelihood, some patients may not have any distinguishable symptoms from the common cold. Consequently, it is important to recognise other ways to diagnose Influenza A or the flu in order to get the proper treatment. Below, this article explores the history of the flu, distinguishable symptoms of H3N2v in humans, what makes the flu difficult to treat, and how to raise awareness in preventing flu spread. 

History and biology

What is the Flu?

The flu is caused by many subtypes of viruses called influenza viruses. Influenza viruses can be specific to certain species of animals and are named depending on the type of protein exposed on the virus's surface. There are several classifications of the flu: Influenza A, Influenza B, Influenza C, and Influenza D.¹ Both Influenza A and B affect humans and do so during particular seasons. The proteins on the surface of the viruses are called haemagglutinin (HA) and neuraminidase (NA), and there are 18 different types of haemagglutinin and 11 different types of neuraminidase (i.e., ranges of H1–18 for and N1–11).¹

Influenza variant naming 

Influenza A-type viruses are named using the type of HA and NA protein (using only the first letter from the abbreviation, H and N), examples include H1N1, H1N2v and H3N2v. Influenza B-type viruses are named based on their origin/lineage, for example, influenza B Yamagata and influenza B Victoria. According to the CDC, infections from Influenza C types are mild and do not generally cause human epidemics, while Influenza D types affect animals apart from humans. Variant type influenzas (denoted by the v after the virus name, e.g. H3N2v) indicate that it is a virus that has changed, more specifically, that the virus can infect humans (in comparison to viruses that can only infect animals such as pigs or birds) (CDC) In the case of H3N2v, the virus initially originated from pigs (swine), but also includes biological characteristics of bird flu. 

Virus biology of influenza viruses

Viruses, to some scientists, do not fulfil the criteria for being ‘living’ organisms.² This is because they cannot do the biological processes in ‘living’ organisms without being inside a host cells. Once a virus is inside a host, they can use the host’s cellular machinery to replicate and invade the rest of the host’s cells.²

Influenza A and B have similar biological properties; both are RNA (Ribonucleic Acid) viruses [as opposed to DNA or deoxyribonucleic acid] that have genomes that are segmented into eight genes that are each surrounded by a ribonucleoprotein complex.^3,4 These ribonucleoprotein complexes are responsible for the ability of the virus to survive and replicate the host and prevent the virus from degrading from the host’s immune system.⁵

These eight gene segments are responsible for the virus’ survival and comprise the following (in no particular order):⁶

1. Basic Polymerase 2 (PB2)
2. Basic Polymerase 1 (PB1)
3. Acidic Polymerase (PA)
4. Nucleocapsid protein (NP)
5. Haemagglutinin (HA)
6. Neuraminidase (NA)
7. Matrix structural protein (M1) and Ion channel protein (M2)
8. Nonstructural protein (NS1), nucleic export protein (NEP, previously NS2)

The first three segments produce the polymerase proteins PB2, PB1 and PA.^7,8 These polymerase proteins are smaller subunits that comprise the virus’ RNA polymerase. The polymerase can then transcribe the virus’ genes that encodes for other proteins needed for its survival and the replication of the RNA genome to exponentially spread to other cells.⁷

The fourth and sixth segments are responsible for the production of HA and NA. HA binds to host receptors (large molecules on the surface of cells) called sialic acid residues that allow the viral and host membrane to fuse together and cause further spread of the virus.⁹ NA are responsible for cleaving (i.e., removing) sialic acid residues and releasing viral particles (virions).¹⁰ Segment 5 encodes for NP, which aids in packing and organising RNA with the polymerase proteins, again aiding in replication.⁹

M1 and M2 are made from transcribing segment seven.⁹ These proteins structure the virus (morphology) and interact with other proteins (M1 with HA and NA; M2 with ribonucleoprotein complexes) to aid in the infection cycle/release of virions.^11,12 The last gene segment forms the protein NS1 and NEP, important proteins that help the virus evade the immune system. NS1 is an antagonist, i.e., it can prevent the production of important immune cells (particularly interferons) that alert the body to infection¹³. NEP can use the host’s (in humans, the NFX1 pathway) proteins to package their viral ribonucleoproteins, disrupting the host’s normal cellular activity.¹⁴

Antigenic drift and shift

More importantly, in evading the immune system, viruses generally have higher mutation rates when transcribing their genes due to their lack of ‘proofreading’ ability.¹⁵ When transcribing our genes, humans have measures to correct for errors.^16,17,18 This inability to proofread during/after transcription in viruses leads to different proteins being made. These proteins include antigens, which are present on the virus's surface.¹⁵ Ideally, if these antigens did not change, our immune systems could recognise them and prevent the spread of the virus. However, due to the high mutation rate of viral transcription, every replication cycle will lead to different antigens (‘drift’), making it difficult for the immune system to recognise the virus.^17,18,19 This antigenic drift is gradual and accumulates over time. This differs from antigenic shift.²⁰

Antigenic shift is not due to the proofreading errors during transcription instead, it is a mutation in the gene segments that code for HA and NA²⁰. This is, therefore, an abrupt and significant change. As such, antigenic shifts are responsible for Influenza A viruses (only since Influenza A viruses have the largest number of host species) being able to transfer to different animals (CDC).²⁰ It is important to note that antigenic shift is infrequent compared to antigenic drift. Thus, the likelihood of a flu pandemic is low (the latest being the H1N1 in 2009). 

H3N2v symptoms

Symptoms of H3N2v are not specific and include one or more of the following (Virginia Department of Health):

• Fever 
• Cough 
• Runny nose
• Body aches
• Nausea
• Vomiting
• Diarrhoea

It may be useful to compare flu symptoms between the common cold and Sars-CoV-19 (COVID-19). A table below shows the frequency of symptoms between the three viruses, but please note that it will differ by individual (obtained from Mayo Clinic sourced from CDC and WHO).

Table 1. Comparison between COVID, Cold and Flu Symptoms and their Frequency

Diagnosis, treatment and vaccination

Diagnosis of influenza is through a swab test; generally a throat or nasal swab is used (and more recently can be done with rapid testing kits), which will show whether you are positive for influenza or not. If you test positive for the flu, your GP can advise you about flu remedies. The NHS notes to be careful with taking multiple medications that may contain paracetamol as it may be possible to overdose. Please also consider that viral infections are NOT the same as bacterial infections, and antibiotics will NOT treat the disease. 

The NHS also offers flu vaccinations between autumn and early winter. The following populations below can receive free flu vaccinations (NHS):

• If you are 65 or over
• Chronic or long-term illness
• Pregnant
• Living in a care home
• If you are the main carer for an older or disabled person
• If you receive a carer's allowance
• If you live with someone who has a weakened immune system
• If you are a frontline health worker or a social worker

However, the CDC also notes that vaccinations for H3N2 viruses might have lower effectiveness due to the higher mutation rate the virus has in comparison to other Influenza A viruses. This leads to more antigenic changes that are not accounted for when the vaccine is approved. Nevertheless, if you are an at-risk patient, the vaccine is still worth taking because it still has the potential efficacy to reduce severe symptoms. 

Summary

Influenza A is an overarching term that includes different virus subtypes. Influenza A-type viruses are named based on the haemagglutinin (HA) and neuraminidase (NA) types present on the virus's surface, and include examples such H1N1 and H3N2v. Viruses can replicate and produce proteins using the host’s cellular machinery and evade the immune system’s response using antigenic drift. On the other hand, the antigenic shift is the abrupt change of HA and NA proteins present in the cell, which can lead to major pandemics due to the ability to cross over to different species. Currently, flu treatments are restricted to treating the symptoms, although the flu vaccine can generally prevent individuals from getting the flu. For H3N2v, vaccines may not be as effective, but if you are an at-risk patient, it is still worth the consideration.