What does mpox do to the body?

What kind of virus is mpox, and how does it get into the human body? Geoff Smith is a leading expert on poxviruses at the University of Oxford…

Geoff - So monkeypox is a pox virus and a member of the orthopoxvirus genus. So other members of that genus include variola virus that causes smallpox, cowpox, and vaccinia virus, which was the vaccine used to eradicate smallpox. And these are all big DNA viruses that replicate in the cytoplasm and are quite closely related genetically. So that infection with one will confer subsequent protection against infection by any other member of that virus genus.

Chris - Where do these viruses normally hang out? I know we call it monkeypox, or now we've rebranded it mpox. Is that a misnomer? Because allegedly monkeys are not the host?

Geoff - Yes, it's a misnomer. It was called monkeypox virus because it was isolated first from a monkey, but that's not the natural reservoir and the exact reservoir is not known, but they're likely to be rodents in different parts of Africa, either Central Africa or West Africa.

Chris - So what is the biology of the virus then? If it's normally in these rodents, what do we think the normal pattern is in terms of it spreading to other creatures, causing disease, et cetera?

Geoff - Well, presumably in the rodents in which it is endemic, it won't cause devastating disease because if it did, then it would kill all the hosts and it wouldn't be able to survive. But monkeypox virus has got a wide host range and can clearly infect other animals, including primates and us. And it's the ability of the virus to spread from the natural rodent reservoir to humans. That is the problem.

Chris - And people talk about there being different variants or versions of these clades. What does that mean and where are they?

GGeoff - Well, there are broadly two clades that are separated geographically. And the clade 1 viruses that originate from Central Africa, such as the Democratic Republic of the Congo, are more virulent than the clade 2 viruses that come from West Africa and which cause less disease in humans. So they're defined by their genetic relatedness, by sequencing the genomes you can tell quickly to which clade a monkeypox virus belongs.

Chris - When they cause disease in an individual, whether that's a monkey or us, how do they spread between individuals do we think?

Geoff - The spread between individuals has always required close contact? So generally, when monkeypox was causing small, sporadic outbreaks in Africa, the outbreaks tended to be self-limiting because the virus did not spread efficiently from person to person. So you may get one or two or three transmissions within a close group, possibly within a family, but it would not go further than that. And so the infections would die out and be self-limiting. And then in 2022, when this big epidemic started, it went global and the viruses originally came from West Africa. The virus then got into the population of men who have sex with men. And so the virus was transmitted by sexual means, and the biology of the virus hadn't changed. It's just that sexual contact is one form of close contact and that's how the virus was spread.

Chris - And once a person catches it, what's it actually doing in the body? What's the process or the mechanism by which it causes disease?

Geoff - Well, that hasn't been looked at in great detail in humans, but it gives a disease which looks very similar to smallpox in that the virus will enter either via a skin abrasion or possibly by the respiratory tract. And then after a series of replication events, it will spread through the body and eventually go to the skin where the characteristic skin blisters are formed. And it's from those skin lesions, either on the skin or in the oropharynx, that the virus can be spread to be transmitted to new people.

Chris - So how does it make a person ill, can it get into almost any cell type in the body or is it hitting a limited repertoire of tissues? And when it does, why does a person actually get the symptoms that they get? Do we know?

Geoff - No, we don't really know the details of that. But the virus can clearly infect a range of cells, including epithelial cells, but likely also white blood cells that it may be able to spread via those throughout the body.