Her early research was on the cattle disease,
bovine viral diarrhoea. Nuttall found that the bovine viral diarrhoea virus was often present as a contaminant in
foetal bovine serum, a commonly used laboratory reagent, a result that was published in
Nature in 1977. She then worked with ornithologist
Chris Perrins trying to identify the virus responsible for
puffinosis, a disease that affects the
Manx shearwater (
Puffinus puffinus) sea bird. During this research, Nuttall visited sea-bird colonies and became interested in
ticks,
arthropods that often infest sea birds as well as other vertebrates, and can act as
vectors for disease. These results challenge the then-accepted idea that arthropod-transmitted viruses can only be transmitted when the arthropod vector feeds on an infected host in which the virus is replicating and circulating in the blood above a threshold level. – and important in natural transmission. Nuttall's group has continued to study the phenomenon, and have shown that
immunity to tick-borne encephalitis virus does not prevent nonsystemic transmission.
Tick saliva Nuttall's recent work has focused on discovering the function of tick saliva's many constituents, as well as the mechanisms by which tick-transmitted pathogens use them to enhance their transmission. In 1998, she and her colleagues characterised three
immunoglobulin-binding proteins, which were among the first proteins from tick saliva to be sequenced. With Norbert Fuchsberger, Valeria Hajnicka and others, Nuttall has shown that tick saliva suppresses the host's antiviral
immune responses, including
natural killer cell activity and the induction of
type I interferon and
cytokines involved in
inflammation. For example, with Guido Paesen, Nuttall has characterised histamine-binding proteins that can suppress inflammation in humans by binding directly to
histamine, rather than blocking its access to cell receptors, of which at least four are known. One of these proteins, rEV131, was investigated by NERC spin-off company Evolutec for the treatment of
hay fever and for use in recovery from
cataract surgery. Tick saliva products are also possible targets for
vaccines to control tick infestation and, potentially, to prevent the diseases they carry. One vaccine candidate explored by Nuttall's group is 64TRP, a 15 kDa
Rhipicephalus appendiculatus protein from the cement cone that glues the tick's mouthparts to the host. Vaccination with 64TRP can protect against tick-borne encephalitis virus carried by a different type of tick, the
castor bean tick (
Ixodes ricinus), in a mouse model. ==Awards==