virology blog
About viruses and viral disease
Daniel Griffin provides a clinical update on COVID-19, then Sabra Klein joins us to discuss the effect of sex, gender, and age on viral infectious disease, including COVID-19.
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Show notes at microbe.tv/twiv
The Beacons of Viral Education (aka the TWiVoners) reveal a cost of being a male mouse – the Y chromosome regulates their susceptibility to influenza virus infection.
You can find TWiV #441 at microbe.tv/twiv, or listen below.
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Disease and death caused by influenza virus are greater in human females than in males. But disease is more common in males from birth through age 15, after which more females are affected. In mice, genetic variation in the Y chromosome controls susceptibility to influenza virus infection (link to paper). Increased susceptibility does not correlate with increased viral replication, but an expanded pathogenic immune response in the lungs.
A panel of mice (strain B6) with the Y chromosome from eleven different strains were used to determine the effect of infection. The mice fell into two groups with distinct high and low survival after intranasal infection with the mouse-adapted PR8 strain of influenza virus. These results show that variation in the Y chromosome influences survival after infection. Furthermore, the previously reported greater susceptibility of female B6 mice to influenza virus infection compared with male mice is due to the presence of the Y chromosome.
Viral replication in the lung does not differ between mouse strains with high and low mortality. Increased mortality is associated with an increase in a type of T lymphocyte called gamma-delta T cells which produce interleukin 17. The latter is known to provoke lung-damaging inflammation.
Differences in susceptibility of mice with different Y chromosomes has nothing to do with the immunosuppressive effects of testosterone. Exactly which genes on the Y chromosome affect influenza virus susceptibility are unknown. Analysis of RNA expression revealed differences in levels of small RNAs in mice of higher versus lower susceptibility. This observation raises the possibility that the Y chromosome might have global effects on gene expression from other chromosomes, which in turn influences susceptibility to infection.
Others have found that the Y chromosome regulates the speed of progression to AIDS in HIV-1 infected men. It seems likely that the Y chromosome has an important general role in modulating the pathogenesis of infectious diseases. A better understanding of how the Y chromosome regulates the expression of other genes will be needed to understand these effects.
The TWiVites discuss Zika virus seroprevalence in wild monkeys, Zika virus mRNA vaccines, and a gamete fusion protein inherited from viruses.
You can find TWiV #432 at microbe.tv/twiv, or listen below.
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The title of a Eurosurveillance article, “An autochthonous case of Zika due to possible sexual transmission, Florence, Italy, 2014” was written to make the headlines. The title should be “An autochthonous case of Zika due to person to person contact, Florence, Italy, 2014.”
An Italian man returns from a 10 day holiday in Thailand and a day later develops a rash with fever and headache. Within 6 days the rash has subsided. About two weeks later his girlfriend develops a similar disease. As this was 2014 no one looked for Zika virus and both were presumed to have dengue virus infection.
The serum samples taken from the patients were pulled from the freezer after Zika virus becomes a household word in 2015. Both patients’ sera are shown to contain neutralizing antibodies against Zika virus, with a clear rise between samples taken early in illness and after recovery.
Apparently the couple had sex between the time the man’s rash subsided, and the onset of the girlfriend’s symptoms. The authors of the paper conclude that transmission by semen is suggested.
Inexplicably, the authors write:
Other transmission modalities (i.e. direct contact with other bodily fluids) are unlikely to play a role but may not be completely ruled out.
Why is it unlikely that the man had a residual rash, possibly leaking virus, which he then transferred to the woman, perhaps on one or more mucus membranes? This mode of transmission is also known as ‘close contact’ between individuals. I am waiting for a similar case report in which the couple used condoms, yet Zika virus infection was still transmitted.
Like everyone else, the authors are seduced by the possibility of sexual transmission of Zika virus. I have yet to see any clear, convincing evidence of sexual transmission of Zika virus. At worst, the risk is extremely low, although probably not zero, given that Zika virus RNA (not virus) has been found in semen of one individual. Consider these facts and act accordingly.