Beating Flu Season

Key takeaways:
~ Some people are more susceptible to different flu strains than others.
~ Tamiflu may not work as well for people with certain genetic variants.
~ There are well-researched, natural options for fighting the flu that you may want to have on hand.

Members will see their genotype report below, plus additional solutions in the Lifehacks section. Consider joining today 

Flu season, genes, and solutions:

The flu goes around each year — usually in November/December and then again in Feb/March in the Northern Hemisphere. Some years it seems worse than others. For the past decade, with the flu vaccine available, 10 to 40 million people in the US have gotten the flu each year.[ref]

How do you know if it’s the flu?

If you are wondering whether it is the flu, Covid, or another virus, you could get tested for both the flu and Covid to see which one it is. The CDC website states you can’t tell them apart by symptoms.[ref]

Flu symptoms include:

  • Fever, chills
  • Fatigue
  • Body ache
  • Cough
  • Sore throat
  • Stuffy nose
  • Headache

Four types of flu viruses have been identified: Influenza A, B, C, and D.

Influenza is a negative-strand RNA virus in the family Orthomyxoviridae. Within each type, multiple strains are going around each year.[ref][ref] The exact flu strain changes each year by recombining parts of different strains.

  1. Influenza A (H1N1 or H3N2): Sometimes called swine flu, this variant usually arises from recombining H1N1 strains from birds, pigs, and humans.[ref]
  2. Influenza B: About 20-30% of flu infections each year are influenza B strains.[ref]
  3. Influenza C: Usually causes mild respiratory illness or is asymptomatic. Most people have antibodies to influenza C by the time they are teens.[ref]
  4. Influenza D: Mainly circulates in cattle and pigs.[ref]

So far this year (fall/winter 2022), about 30% of cases are influenza A(H1N1), with the rest being influenza A(H3N2).[ref]

Interestingly, several studies show that the majority of people exposed to a new flu strain don’t get the flu, or at least don’t get any symptoms. A study on the swine flu pandemic (2009) noted the “majority of people newly exposed to one of the most dangerous viruses to circulate in human populations in recent history… did not notice any symptoms.”[ref]

We have robust immune systems which fight off viruses in multiple ways. Plus, we all have slight genetic differences in immune system genes, giving some an advantage for certain flu strains.

Differences in immune system genes are a feature allowing parts of a population to survive new pathogens.

Cell entry and replication:

With Covid in the news for the past few years, we have all gotten a crash course in SARS-CoV-2 virology and how the virus enters the cell via the ACE2 receptor.

The flu virus is not as picky about needing a specific type of cell receptor for entry.

Hemagglutinin is a cell surface protein on the influenza virus that helps it to attach to the host cell. It attaches to glycans called sialic acid on the surface of cells in the respiratory tract.[ref] Sialic acids cause a negative charge on cell surfaces and help keep water at the cell’s surface. Thus, they are found in areas with a mucous membrane – such as the nose, lungs, and intestines. And this is where the flu virus easily enters the cell by endocytosis and replicates.

Inside the cell, the flu virus makes its way to the cell nucleus, where it uses the host’s RNA replication enzymes to transcribe the viral proteins for replication.[ref]

Transmission of the flu:

The flu is an airborne virus, spreading via aerosols and probably by direct contact.[ref]

Airborne transmission is defined as inhaling infectious viruses smaller than 5 μm at distances greater than 3-6 feet from the infected individual.

Influenza, RSV, rhinovirus, SARS-CoV, MERS, and Covid are all spread this way. Viral aerosol particles can linger in the air for hours to days.[ref]

Understanding airborne viruses can help explain how the flu is transmitted between people and why it is seasonal…

Why is the flu seasonal?

The question of why the flu always goes around about the same time in a region has puzzled researchers for years. There are theories on vitamin D levels, UV light changes, seasonal movement, and humidity changes.

For humidity, the theory is that lower humidity allows the flu aerosol particle size to become smaller and remain in the air longer. Viruses have specific humidity ranges where they are likely to linger in the air and be breathed in by people.

But seasonal relative humidity changes don’t tell the whole story. What feels like a humid day in Grand Junction, CO, would be considered a very dry day in Charleston, SC.

A recent study points towards the combination of humidity changes along with changes to the mucus membranes of people living in the area.

Take Florida, for example. For people whose noses and mucus membranes were used to more humidity, a drop in humidity will feel dry, and there will be changes to the mucus production in the noses adapted to the area. Similarly, Wyoming may always have less humidity than Florida’s driest day, but a change from 15% relative humidity to 8% will dry out Wyoming noses.[ref]

Genetics is the other key to who gets the flu, so let’s dig into the genes identified in research studies.


Flu Genotype Report:

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Genetic variants can increase or decrease your susceptibility to getting sick from viruses and bacteria.

Genetic variants affecting susceptibility to H3N2 strains:

IL17 gene: Encodes interleukin 17, a pro-inflammatory cytokine produced by T helper cells.

Check your genetic data for rs2275913 (23andMe v4, v5)

  • G/G: typical risk for H3N2 flu (compared to A/A)
  • A/G: typical risk for H3N2 flu (compared to A/A)
  • A/A: half the risk for H3N2 flu[ref], increased IL17[ref]

Members: Your genotype for rs2275913 is .

IL1B gene: encodes interleukin 1B, another pro-inflammatory cytokine

Check your genetic data for rs16944 (23andMe v4, v5):

  • A/A: typical risk for H3N2 flu
  • A/G: typical risk for H3N2 flu
  • G/G: less than half the risk for H3N2 flu[ref][ref]

Members: Your genotype for rs16944 is .

IL28 gene: encodes interleukin 28

Check your genetic data for rs8099917 (23andMe v4, v5):

  • T/T: typical risk for H3N2 flu
  • G/T: half the risk for H3N2 flu
  • G/G: half the risk for H3N2 flu[ref]

Members: Your genotype for rs8099917 is .

Genetic variants impacting H1N1 susceptibility:

CCR5 gene:
The CCR5 gene codes for a protein on the surface of white blood cells. CCR5 is a chemokine receptor involved in our immune response. People who carry the CCR5delta32 variant are more resistant to HIV infection.

The CCR5delta32 variant has also been investigated in H1N1 flu cases. Several studies have found a link to susceptibility and increased severity of flu symptoms for people who carry the variant.[ref][ref] But, not all studies agree.[ref]

Check your genetic data for i3003626 (23andMe v4, v5 [also known as rs333 and CCR5delta32]):

  • II: typical
  • ID: possibly higher risk of flu or increased severity of flu[ref][ref]
  • DD: resistance to the common strains of HIV, possibly higher risk of increased flu severity

Members: Your genotype for i3003626 is .

Severity of the flu:

Getting the flu is one thing… No one ever wants to be sick. But you really don’t want to have a severe case and end up in the hospital. Everything needs to be balanced with your immune response – enough to kill off the virus, but not an over-activation of your immune system. Genetic variants in the immune system are linked to causing a more severe immune reaction to the flu.

CD55 gene:
The CD55 gene codes for the complement decay-accelerating factor, which regulates the complement system. A variant of CD55 has been associated with the severity of H1N1 infection.[ref]

Check your genetic data for rs2564978 (23andMe v4):

  • C/C: typical severity of flu
  • C/T: typical severity of flu
  • T/T: increased severity of H1N1 flu infection[ref][ref]

Members: Your genotype for rs2564978 is .

MBL2 gene: codes for mannose-binding lectin, which activates the complement system.

Check your genetic data for rs1800450 (23andMe v4, v5; AncestryDNA):

  • C/C: typical
  • C/T: likely to have lower mannose-binding lectin protein complex levels[ref], less likely to have severe H1N1[ref]
  • T/T: mannose-binding protein deficiency[ref], greater risk of staph, MRSA, tuberculosis[ref][ref][ref], less likely to have severe H1N1[ref]

Members: Your genotype for rs1800450 is .

FCGR2A gene: encodes a part of IgG antigen

Check your genetic data for rs1801274 (23andMe v4, v5; AncestryDNA):

  • A/A: 2x relative risk of severe pneumonia in H1N1 flu[ref]
  • A/G: increased relative risk of severe pneumonia in H1N1 flu
  • G/G: typical risk

Members: Your genotype for rs1801274 is .

Genetics and Tamiflu:

If you get the flu and go to the doctor, one medication they may offer is oseltamivir, which is the generic name for Tamiflu.

Oseltamivir (Tamiflu) is a prodrug converted by the CES1 enzyme into an active drug. Some people have genetic variants that decrease the function of the CES1 enzyme. Women naturally seem to have greater CES1 activity than men, so the effects of the genetic variant may be intensified for men.

CES1 gene: converts Tamiflu into an active drug.

Check your genetic data for rs71647871 (23andMe v4, v5; AncestryDNA):

  • C/C: typical
  • C/T: 60% decreased CES1 enzyme function;
  • T/T: more than 60% decreased CES1 (rare genotype)[ref]

Members: Your genotype for rs71647871 is .

Check your genetic data for rs121912777 G428A (23andMe v5; AncestryDNA):

  • C/C: typical
  • C/T: significantly decreased CES1 enzyme function (rare genotype)[ref]
  • T/T: significantly decreased CES1 (rare genotype)

Members: Your genotype for rs121912777 is .

ABCB1 Genetic Variants:

In addition to the conversion of oseltamivir into the active component by CES1, another genetic component is in play here.

The ABCB1 gene codes for a transporter that moves foreign substances back out of a cell. Essentially, cells need to spit the toxins back out. When it comes to medications, the ABCB1 genetic variants that increase the gene’s activity can actually be a problem because the drug doesn’t stay in the cell.

Check your genetic data for rs1045642 C3435T (23andMe v.4 only)

  • A/A: reduced drug efflux (out of the cell), may need lower dosages of some drugs in comparison to those with GG[ref][ref], Increased risk of adverse events with oseltamivir[ref]
  • A/G: intermediate efflux, no increase in adverse events with oseltamivir
  • G/G: greater efflux (out of the cell) for drugs and toxins, no increase in adverse events with oseltamivir

Members: Your genotype for rs1045642 is .


Lifehacks:

You wake up with muscle aches and a fever… What are your options? The research studies are presented here so you can decide what is best for you.

Research on Natural Solutions for the Flu

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About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and also an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.