As any of you who have children, in fact anyone who has ever met, seen or been a child, there are all sorts of things up their noses, fingers, Lego pieces, but more importantly viruses. They are awash with different viruses. We are particularly interested in the effect of one viral infection on another.
We investigated this in the context of a vaccine study.
There is an influenza vaccine that is live, but genetically weakened; called
live attenuated influenza vaccine or LAIV. This vaccine is sprayed up the noses
of children where it causes a limited infection that can train the immune
system and protect against future influenza infections. This gives us a safe
way to explore how flu infections happen in children and what factors affect
infections particularly the immune response. This study was performed in The
Gambia by Dr Thushan de Silva.
In our recent study: Prior
upregulation of interferon pathways in the nasopharynx impacts viral shedding
following live attenuated influenza vaccine challenge in children we looked
at the influence of the presence of other infections on LAIV infection. The
first thing we measured was the presence of viruses in children – remarkably
42% of children had detectable viral RNA. This reflects other studies we have done where
we saw that 20% of children had another viral infection. For the analysis we
then compared the responses in children with and without another infection and
what impact this had on how well the LAIV viruses could establish a local
infection in the nose .
In particular, we were interested changes in the genes in
the nose due to infection with other viruses. These changes in genes give us a
more global sense of the response to infection. What we are actually measuring
are changes in RNA levels, called the transcriptome. We can group the
individual genes into families based on their function. We are particularly
interested in genes associated with the immune response.
What we observed in our study was that children who had another
infection at the time of LAIV immunisation had far greater levels of genes
associated with signalling through a pathway called type I interferons. These
genes are part of the innate immune response to infection and switch on an
antiviral state, which makes it more difficult for other viruses to infect
them. In line with this, children with higher levels of the anti-viral genes
had lower LAIV viral replication.
These findings might help us understand differences in
outcome following infections such as flu and how other viral infections
immediately before exposure could influence this.
