Why do men get worse symptoms? Hero Images/Getty

Is man-flu a quirk of viral evolution? Some viruses might cause weaker symptoms in women than in men because it makes them more likely to spread.

Many infections cause more severe illness in men than women. Men infected with tuberculosis are 1.5 times more likely to die than women; men infected with human papillomavirus are five times more likely to develop cancer than women; and men infected with Epstein-Barr virus are at least twice as likely to develop Hodgkin’s lymphoma as women.

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Many think this pattern is because of differences between the sexes’ immune systems. But another explanation is that women are more valuable hosts. Women can pass infections to their children during pregnancy, birth and breastfeeding, so there’s an evolutionary pressure on viruses to be less harmful to them, say Francisco Úbeda and Vincent Jansen at Royal Holloway University of London.


Mother to child

In order for a virus to infect others, it needs to produce more copies of itself in the body. Making their host ill is an unavoidable consequence of this. “That’s not something a pathogen particularly sets out to do because it’s shooting itself in the foot, should it have one,” says Jansen.

The researchers used mathematical modelling to show that, for pathogens that affect both sexes, natural selection in theory should favour those that cause less illness in women – as long as they can be transmitted from mother to child.

This evolutionary pressure, they argue, could explain a longstanding puzzle: why human T-cell lymphotropic virus type 1 (HTLV-1) progresses to leukaemia much more commonly in Japanese men than Japanese women, but affects both sexes equally in the Caribbean. They argue that this discrepancy is because women breastfeed their babies more commonly and for longer in Japan – giving the virus more opportunity to enter another host.

For this to be the case, though, the virus would have to be able to detect whether it’s inside a man or a woman. We don’t yet know how it would do this, but it’s not impossible, says Jansen. “There are all sorts of hormonal and other pathways that are slightly different between men and women,” he says.

If we were to identify a mechanism, that would open the possibility of manipulating it. “We could try to make the virus think it’s in a female body rather than a male body and therefore take a different course of action,” says Jansen.

Sex differences

The study emphasises the need to conduct clinical trials in both sexes, rather than predominantly in men as is often the case, says David Duneau, an evolutionary biologist at the University of Toulouse, France. “The parasites themselves are behaving differently in males and females, so we need to know what they do in both sexes,” he says.

It’s refreshing to consider pathogen evolution as an alternative explanation for sex differences in diseases, says Sabra Klein, who researches differences in immune responses at Johns Hopkins Bloomberg School of Public Health, Baltimore. But she says the model’s assumptions about HTLV-1 transmission in Japan and the Caribbean ignore other variables – such as ethnicity or culture – that could also be involved.

Jansen now plans to look at animal diseases, such as retroviruses that cause cancer in chickens. “When flocks of chickens are infected with a particular virus, we see that more of the male chickens develop tumours than females,” he says.

Could selection pressure on viruses bolster men’s claims that they are affected more strongly by colds or flu? It wouldn’t be expected, says Jansen, as mother-to-child transmission isn’t an important route for flu viruses. “To me, man-flu sounds like an excuse for men not to go to work,” he says.

Journal reference: Nature Communications, DOI: 10.1038/ncomms13849