Why does hand foot and mouth disease (coxsackievirus) cause blisters in the hands, feet, and mouth?

Submitted by aubergine_alibi_ t3_yy1r0r in askscience

I saw a post about chickenpox in this sub and the common spots, but this made me wonder why hand foot and mouth disease (coxsackievirus A16) specifically causes blisters and rashes on these extremities. I am not well versed in virology or histology, so if this belongs in another sub please let me know (like r/Nodumbquestions) Thank you!!

Edit: Y’all I know WHY it’s called Hand foot and mouth 😭 thank you for clarifying. I’m asking WHY the blisters form on the hands, feet, and in the mouth rather than indiscriminately all over the body, such as with other viruses like varicella (chickenpox)

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the_dan_man t1_iwsl3zh wrote

In order for a virus to infect a cell, it has to be able to bind to one or more receptors on the cell's surface (often proteins on the cell's surface, but can be other things like specific lipids in the cell membrane, or carbohydrates on the membrane's surface) and use them as a foothold to somehow deliver its genetic information into the cell.

If a cell doesn't have the right receptors on its surface, the virus can't grab on to them, and that affects which kinds of cells it can infect. For instance, HIV uses receptors such as CCR5 and CXCR4 to enter certain kinds of white blood cells - cells that don't have those receptors, (e.g. pretty much any other kind of cell in our bodies) can't be infected by HIV. Changes in the receptor's structures can also affect binding ability - for instance, you may have heard about people who are naturally resistant to HIV because they have a mutation in CCR5.

It's also worth noting that successful infection often requires successful interactions with multiple different kinds of receptors and not just a single one - so if a cell doesn't have the right mix of other receptors on its surface, it may not get infected even if it also has what researchers have determined to be the "primary" receptor.

Presumably, the epithelial cells in the hands, feet, and mouth just happen to have the right mix of receptors that enable infection by coxsackievirus A16 (or enterovirus 71, the other main virus that can cause hand, foot, and mouth disease). This paper says a protein called SCARB2 is a receptor used by both coxsackievirus A16 and enterovirus 71, and this paper indicates that certain carbohydrates on the cell membrane are also necessary for infection by coxsackievirus A16.

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[deleted] t1_iwsybjd wrote

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semvhu t1_iwt305i wrote

Would you know if cells on the retina or other parts of the back of the eyeball can be affected by this virus? In June of last year, I caught a pretty good case from my 2 year old grandson. I ended up with lots of spots on my face, hands, and feet. About a month after I got symptoms, I noticed a new blind spot in my left eye vision. A specialist found a spot on my retina that looked inflamed and damaged. He had no explanation for it other than the virus might have caused it.

The only connection I knew of was this virus, but perhaps it was coincidence.

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gvna69 t1_iwufaky wrote

I did some quick browsing and it seems coxsackie can infect the eye and cause conjunctivitis, uveitis and other complications.

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ashpatash t1_iwv9aqw wrote

Yea it can cause acute hemorrhagic conjunctivitis. Just had it in our house, looked terrifying but surprisingly painless.

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MisuseOfMoose t1_iwu5f1s wrote

This phenomenon is referred to as tissue tropism, for those wanting to learn more.

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HangryPete t1_iwsz3t7 wrote

SCARB2 is also on a lot of liver and circulating blood cells. It's a fatty acid uptake mechanism. Very interesting.

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kitzdeathrow t1_iwue18s wrote

>For instance, HIV uses receptors such as CCR5 and CXCR4 to enter certain kinds of white blood cells

Maybe a pedantic nitpick. But CCR5 and CXCR4 are specifically co-receptors that, in general, define which type of CD4+ T-cells the virus can infect. The CD4 receptor is the primary surface protein recognized by the HIV env protein.

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oldpaintunderthenew t1_iwtrq9v wrote

Really interesting! Does it have anything to do with the fact that the skin on hands/feet/lips is different in that it has no hair follicles?

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thor_barley t1_iww7tom wrote

One of my kids had a horrible case and it was all over his wrists and the back of his hands. Also while it’s generally referred to as HFM it should be called HFMB, or hand, foot, mouth and butthole area.

I just had it and the spots felt like itchy pins and needles. Not painful if left alone but knocks and bumps were very painful. I could feel the tingling behind my index fingernails (you can lose finger and toenails some time after getting the virus, although it hasn’t happened yet). The whole of my back was similarly tingly. I didn’t get around to taking any pictures of my butthole area unfortunately.

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Jupiter642 t1_iwtpyqa wrote

It seems we are really lucky, that there is only one virus out there who detected the right mix to attack our white blood cells.

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Kirk_Kerman t1_iwuyjv0 wrote

There's actually a few. human T-cell lymphotropic virus is another. Infects T-cells and causes leukemia in about 5% of infections.

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Tyrssons t1_iwvhdj7 wrote

To build on this, it is actually quite common.

EBV and CMV are herpes viruses that attack immune cells, measles attacks lymphocytes, salmonella likes to live in macrophages.

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aubergine_alibi_ OP t1_iws4tq1 wrote

Sorry if I didn’t make this clear. I’m NOT asking about WHY the disease was named this. I’m asking WHY blisters form where they do with this disease rather than ALL OVER like smallpox and chicken pox

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skeeter_wrangler t1_iwurl0v wrote

You're basically exposed to everything during childhood. No prior immunity plus kids are less hygiene conscious, especially in daycares and schools where there's just a lot of contact. Over time our immunities wane, so even if you had Coxsackievirus at a child, you can get it again. Some viruses change (like influenza) and get around preexisting immunity. Or, for example "rhinoviruses", there exist multiple subtypes of the same virus, so you could get type A in one season and type B the next. Finally, some viruses, like coronaviruses, don't really care about preexisting immunity. They tend to create weak immune memory, so you can just get infected over and over. There are definitely examples of virus-virus interactions, for example having RSV somehow protects you from getting influenza for apparently a long time (at least in mouse studies). But I don't know of any study looking at whether covid interacts with a non respiratory virus.

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