Pat Nuttall

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Patricia (Pat) Anne Nuttall, OBE (born 1953) [1] is a British virologist and acarologist known for her research on tick-borne diseases. Her discoveries include the fact that pathogens can be transmitted between vectors feeding on a host without being detectable in the host's blood. She is also a science administrator who served as the director of the Natural Environment Research Council (NERC) Centre for Ecology & Hydrology (2001–11). [2] As of 2015, she is professor of arbovirology in the Department of Zoology of the University of Oxford. [3]

Contents

Education

Nuttall gained a BSc in microbiology at the University of Bristol in 1974. Her PhD in virology (1978), under the supervision of Jim Stott and C. Kaplan, was at the Institute for Animal Health (now the Pirbright Institute) and the University of Reading. [1] [4]

Career

From 1977, Nuttall did post-doctoral research at the Edward Grey Institute of Field Ornithology of the Department of Zoology at the University of Oxford and the NERC Unit of Invertebrate Virology in Oxford. [1] [4] She remained at the NERC unit, which was renamed the Institute of Virology and Environmental Microbiology (IVEM), rising to be its director in 1996. [1] [4] In 2001, IVEM merged with other bodies to become the NERC Centre for Ecology & Hydrology, and Nuttall served as the centre's director until 2011. [2] During this period she oversaw the major restructuring of the centre. [4] [5] She subsequently directed national projects with NERC. [1] [2] She chaired the Partnership for European Environmental Research from 2008 to 2010. [1] [6]

Nuttall has been professor of arbovirology in the Department of Zoology of the University of Oxford since 2013. [1] [3] She is a fellow of Wolfson College, Oxford. [7]

Research

Electron micrograph of tick-borne encephalitis virus Tick-borne encephalitis virus (crop).png
Electron micrograph of tick-borne encephalitis virus

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. [4] [8] 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. [4] [9] 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. [4]

Nonsystemic transmission

In the early 1980s, Nuttall started to study viruses transmitted by ticks, initially focusing on orbiviruses, nairoviruses and thogotoviruses. [1] While performing experiments designed to explore whether Thogoto virus, an influenza-like virus, can be transmitted between ticks during mating, Nuttall and her colleagues unexpectedly found that control ticks became infected. [4] They discovered that the virus can be transmitted between infected and uninfected ticks when they feed simultaneously on apparently uninfected guinea pigs, without the virus being present at a detectable level in the blood. [10] [11] [12] With Milan Labuda, Nuttall subsequently demonstrated the same phenomenon with tick-borne encephalitis virus, a better-understood arthropod-transmitted virus. [13]

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. [4] [11] [12] [14] Sarah Randolph comments:

Suddenly the conventional wisdom that systemic infections above a certain threshold level were necessary for transmission, and could therefore be used to assay host competence, was over-turned. Viraemia and even bacteraemia are now seen as an inconsistent, species-specific consequence of infection but not a necessary condition for transmission. [12]

The phenomenon of nonviraemic or nonsystemic transmission turns out to be widespread – it has been subsequently observed with many other viruses transmitted by ticks, black flies and mosquitos, including major human pathogens such as West Nile virus, as well as other pathogens, including the spirochaete Borrelia burgdorferi , which causes Lyme disease. [11] [15] [16] – and important in natural transmission. [14] Nuttall's group has continued to study the phenomenon, and have shown that immunity to tick-borne encephalitis virus does not prevent nonsystemic transmission. [17]

Tick saliva

The tropical bont tick, whose saliva is the source of variegin Amblyomma-variegatum-male.jpg
The tropical bont tick, whose saliva is the source of variegin

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. [3] Nuttall and colleagues were the first to show, in 1989, that tick saliva promotes the transmission of viruses, a phenomenon which they have called "saliva-assisted transmission"; this has been suggested as a mechanism for nonsystemic transmission. [4] [12] [18] [19] In 1998, she and her colleagues characterised three immunoglobulin-binding proteins, which were among the first proteins from tick saliva to be sequenced. [12] [20] [21] 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. [4] Her group has also shown that the proteins in saliva differ between individual ticks of the same species and also change over the course of feeding. [20]

Drugs and vaccines

Some components of tick saliva have potential as drugs to treat a range of conditions unrelated to tick disease. [3] [22] Nuttall comments that "These molecules have been refined by millions of years of evolution. There are no toxicity problems, they work on a range of animals, they aren't fragile — and there are an awful lot of them." [22] 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. [4] [22] [23] 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. [4] [22] Another example is the anticoagulant variegin, discovered by Nuttall and Maria Kazimirova in the tropical bont tick (Amblyomma variegatum), which represents a novel class of thrombin inhibitor; it has been shown to prevent venous thrombosis in a zebrafish model. [24] [25]

Tick saliva products are also possible targets for vaccines to control tick infestation and, potentially, to prevent the diseases they carry. [3] [20] 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. [20] [26]

Awards

Nuttall received the Ivanovsky Medal for Virology of the Russian Academy of Sciences in 1996. [4] She was awarded the OBE in the 2000 New Year Honours List, for "services to Environmental Science and Policy." [27]

Selected publications

Books

Research papers

Related Research Articles

<span class="mw-page-title-main">West Nile fever</span> Human disease caused by West Nile virus infection

West Nile fever is an infection by the West Nile virus, which is typically spread by mosquitoes. In about 80% of infections people have few or no symptoms. About 20% of people develop a fever, headache, vomiting, or a rash. In less than 1% of people, encephalitis or meningitis occurs, with associated neck stiffness, confusion, or seizures. Recovery may take weeks to months. The risk of death among those in whom the nervous system is affected is about 10 percent.

<i>Flaviviridae</i> Family of viruses

Flaviviridae is a family of enveloped positive-strand RNA viruses which mainly infect mammals and birds. They are primarily spread through arthropod vectors. The family gets its name from the yellow fever virus; flavus is Latin for "yellow", and yellow fever in turn was named because of its propensity to cause jaundice in victims. There are 89 species in the family divided among four genera. Diseases associated with the group include: hepatitis (hepaciviruses), hemorrhagic syndromes, fatal mucosal disease (pestiviruses), hemorrhagic fever, encephalitis, and the birth defect microcephaly (flaviviruses).

<i>Flavivirus</i> Genus of viruses

Flavivirus, renamed Orthoflavivirus in 2023, is a genus of positive-strand RNA viruses in the family Flaviviridae. The genus includes the West Nile virus, dengue virus, tick-borne encephalitis virus, yellow fever virus, Zika virus and several other viruses which may cause encephalitis, as well as insect-specific flaviviruses (ISFs) such as cell fusing agent virus (CFAV), Palm Creek virus (PCV), and Parramatta River virus (PaRV). While dual-host flaviviruses can infect vertebrates as well as arthropods, insect-specific flaviviruses are restricted to their competent arthropods. The means by which flaviviruses establish persistent infection in their competent vectors and cause disease in humans depends upon several virus-host interactions, including the intricate interplay between flavivirus-encoded immune antagonists and the host antiviral innate immune effector molecules.

<span class="mw-page-title-main">Arbovirus</span> Common name for several species of virus

Arbovirus is an informal name for any virus that is transmitted by arthropod vectors. The term arbovirus is a portmanteau word. Tibovirus is sometimes used to more specifically describe viruses transmitted by ticks, a superorder within the arthropods. Arboviruses can affect both animals and plants. In humans, symptoms of arbovirus infection generally occur 3–15 days after exposure to the virus and last three or four days. The most common clinical features of infection are fever, headache, and malaise, but encephalitis and viral hemorrhagic fever may also occur.

Tick-borne diseases, which afflict humans and other animals, are caused by infectious agents transmitted by tick bites. They are caused by infection with a variety of pathogens, including rickettsia and other types of bacteria, viruses, and protozoa. The economic impact of tick-borne diseases is considered to be substantial in humans, and tick-borne diseases are estimated to affect ~80 % of cattle worldwide. Most of these pathogens require passage through vertebrate hosts as part of their life cycle. Tick-borne infections in humans, farm animals, and companion animals are primarily associated with wildlife animal reservoirs. many tick-borne infections in humans involve a complex cycle between wildlife animal reservoirs and tick vectors. The survival and transmission of these tick-borne viruses are closely linked to their interactions with tick vectors and host cells. These viruses are classified into different families, including Asfarviridae, Reoviridae, Rhabdoviridae, Orthomyxoviridae, Bunyaviridae, and Flaviviridae.

<i>Bunyavirales</i> Order of RNA viruses

Bunyavirales is an order of segmented negative-strand RNA viruses with mainly tripartite genomes. Member viruses infect arthropods, plants, protozoans, and vertebrates. It is the only order in the class Ellioviricetes. The name Bunyavirales derives from Bunyamwera, where the original type species Bunyamwera orthobunyavirus was first discovered. Ellioviricetes is named in honor of late virologist Richard M. Elliott for his early work on bunyaviruses.

<span class="mw-page-title-main">Tick-borne encephalitis</span> Medical condition

Tick-borne encephalitis (TBE) is a viral infectious disease involving the central nervous system. The disease most often manifests as meningitis, encephalitis or meningoencephalitis. Myelitis and spinal paralysis also occurs. In about one third of cases sequelae, predominantly cognitive dysfunction, persist for a year or more.

<i>Tick-borne encephalitis virus</i> Species of virus

Tick-borne encephalitis virus (TBEV) is a positive-strand RNA virus associated with tick-borne encephalitis in the genus Flavivirus.

<i>Alphavirus</i> Genus of viruses

Alphavirus is a genus of RNA viruses, the sole genus in the Togaviridae family. Alphaviruses belong to group IV of the Baltimore classification of viruses, with a positive-sense, single-stranded RNA genome. There are 32 alphaviruses, which infect various vertebrates such as humans, rodents, fish, birds, and larger mammals such as horses, as well as invertebrates. Alphaviruses that could infect both vertebrates and arthropods are referred dual-host alphaviruses, while insect-specific alphaviruses such as Eilat virus and Yada yada virus are restricted to their competent arthropod vector. Transmission between species and individuals occurs mainly via mosquitoes, making the alphaviruses a member of the collection of arboviruses – or arthropod-borne viruses. Alphavirus particles are enveloped, have a 70 nm diameter, tend to be spherical, and have a 40 nm isometric nucleocapsid.

<i>Thogotovirus</i> Genus of viruses

Thogotovirus is a genus of enveloped RNA viruses, one of seven genera in the virus family Orthomyxoviridae. Their single-stranded, negative-sense RNA genome has six or seven segments. Thogotoviruses are distinguished from most other orthomyxoviruses by being arboviruses – viruses that are transmitted by arthropods, in this case usually ticks. Thogotoviruses can replicate in both tick cells and vertebrate cells; one subtype has also been isolated from mosquitoes. A consequence of being transmitted by blood-sucking vectors is that the virus must spread systemically in the vertebrate host – unlike influenza viruses, which are transmitted by respiratory droplets and are usually confined to the respiratory system.

Powassan virus (POWV) is a Flavivirus transmitted by ticks, found in North America and in the Russian Far East. It is named after the town of Powassan, Ontario, where it was identified in a young boy who eventually died from it. It can cause encephalitis, inflammation of the brain. No approved vaccine or antiviral drug exists. Prevention of tick bites is the best precaution.

<span class="mw-page-title-main">Disease vector</span> Agent that carries and transmits an infectious pathogen into another living organism

In epidemiology, a disease vector is any living agent that carries and transmits an infectious pathogen to another living organism; agents regarded as vectors are organisms, such as parasites or microbes. The first major discovery of a disease vector came from Ronald Ross in 1897, who discovered the malaria pathogen when he dissected a mosquito.

<span class="mw-page-title-main">Mosquito-borne disease</span> Diseases caused by bacteria, viruses or parasites transmitted by mosquitoes

Mosquito-borne diseases or mosquito-borne illnesses are diseases caused by bacteria, viruses or parasites transmitted by mosquitoes. Nearly 700 million people get a mosquito-borne illness each year resulting in over 725,000 deaths.

A robovirus is a zoonotic virus that is transmitted by a rodent vector.

Ticks are insects known for attaching to and sucking blood from land-dwelling animals. Ticks fall under the category of 'arthropod', and while they are often thought of in the context of disease transmission, they are also known to cause direct harm to hosts through bites, toxin release, and infestation. Infestation can cause symptoms ranging from mild to severe and may even cause death. Hosts can include any number of vertebrates, though humans and livestock are more likely to be the interest of researchers.

Langat virus (LGTV) is a virus of the genus Flavivirus. The virus was first isolated in Malaysia in 1956 from a hard tick of the Ixodes genus. This virus is antigenically related to Omsk hemorrhagic fever virus, Kyasanur forest disease virus, Alkhurma virus, Louping ill virus and other viruses of the tick-borne encephalitis virus (TBEV) complex. The Langat virus does not pose a significant epidemiological threat in comparison with TBEV. There are no known cases of human diseases associated with LGTV. The Malaysian strain is naturally attenuated and induces neutralizing antibodies to tick-borne encephalitis virus (TBEV) and protection against other TBEV complex viruses in animals.

Royal Farm virus, previously known as Karshi virus, was not viewed as pathogenic or harmful to humans. Although infected people suffer with fever-like symptoms, some people in Uzbekistan have reported with severe disease such as encephalitis and other large outbreaks of fever illness connected infection with the virus.

<i>West Nile virus</i> Species of flavivirus causing West Nile fever

West Nile virus (WNV) is a single-stranded RNA virus that causes West Nile fever. It is a member of the family Flaviviridae, from the genus Flavivirus, which also contains the Zika virus, dengue virus, and yellow fever virus. The virus is primarily transmitted by mosquitoes, mostly species of Culex. The primary hosts of WNV are birds, so that the virus remains within a "bird–mosquito–bird" transmission cycle. The virus is genetically related to the Japanese encephalitis family of viruses. Humans and horses both exhibit disease symptoms from the virus, and symptoms rarely occur in other animals.

<i>Modoc virus</i> Species of virus

Modoc virus (MODV) is a rodent-associated flavivirus. Small and enveloped, MODV contains positive single-stranded RNA. Taxonomically, MODV is part of the Flavivirus genus and Flaviviridae family. The Flavivirus genus includes nearly 80 viruses, both vector-borne and no known vector (NKV) species. Known flavivirus vector-borne viruses include Dengue virus, Yellow Fever virus, tick-borne encephalitis virus, and West Nile virus.

<span class="mw-page-title-main">Climate change and infectious diseases</span> Overview of the relationship between climate change and infectious diseases

Global climate change has increased the occurrence of some infectious diseases. Those infectious diseases whose transmission is impacted by climate change include for example the vector-borne diseases dengue fever, malaria, tick-borne diseases, leishmaniasis, zika fever, chikungunya and Ebola virus disease. One of the mechanisms for increased disease transmission is that climate change is altering the geographic range and seasonality of the insects that can carry the diseases. Scientists stated a clear observation in 2022: "the occurrence of climate-related food-borne and waterborne diseases has increased ."

References

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  2. 1 2 3 "Professor Mark Bailey becomes acting Director of the Centre for Ecology & Hydrology", Centre for Ecology & Hydrology website, Natural Environment Research Council, 1 March 2011, retrieved 16 March 2015
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  5. ↑ House of Commons: Science and Technology Committee, Research Council Institutes: Fourth Report of Session 2006–07, Vol. 2: Oral and Written Evidence, The Stationery Office, pp. Ev47–49
  6. ↑ "METIER Final Conference: Schedule and Lecturers" (PDF), Website, Partnership for European Environmental Research , retrieved 18 March 2015
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  8. ↑ Nuttall PA, Luther PD, Stott EJ (1977), "Viral contamination of bovine foetal serum and cell cultures", Nature , 266 (5605): 835–37, Bibcode:1977Natur.266..835N, doi:10.1038/266835a0, PMID   194159, S2CID   4269062
  9. ↑ Brooke M (2010), The Manx Shearwater, A & C Black, pp. 8, 161
  10. ↑ Jones LD, Davies CR, Steele GM, Nuttall PA (1987), "A novel mode of arbovirus transmission involving a nonviremic host", Science , 237 (4816): 775–77, Bibcode:1987Sci...237..775J, doi:10.1126/science.3616608, JSTOR   1699212, PMID   3616608
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  12. 1 2 3 4 5 Randolph SE (2009), "Tick-borne disease systems emerge from the shadows: the beauty lies in molecular detail, the message in epidemiology", Parasitology , 136 (12): 1403–13, doi:10.1017/s0031182009005782, PMID   19366480, S2CID   22845163
  13. ↑ Labuda M, Jones LD, Williams T, Danielova V, Nuttall PA (1993), "Efficient transmission of tick-borne encephalitis virus between cofeeding ticks", Journal of Medical Entomology , 30: 295–99, doi:10.1093/jmedent/30.1.295, PMID   8433342
  14. 1 2 Lord CC, Tabachnick WJ (2002), "Influence of nonsystemic transmission on the epidemiology of insect borne arboviruses: A case study of vesicular stomatitis epidemiology in the Western United States", Journal of Medical Entomology , 39 (3): 417–26, doi: 10.1603/0022-2585-39.3.417 , PMID   12061433
  15. ↑ Kuno G, Chang GJ (2005), "Biological transmission of arboviruses: Reexamination of and new insights into components, mechanisms, and unique traits as well as their evolutionary trends", Clinical Microbiology Reviews , 18 (4): 608–37, doi:10.1128/cmr.18.4.608-637.2005, PMC   1265912 , PMID   16223950
  16. ↑ Patrican LA (1997), "Acquisition of Lyme disease spirochetes by cofeeding Ixodes scapularis ticks", American Journal of Tropical Medicine and Hygiene , 57 (5): 589–93, doi:10.4269/ajtmh.1997.57.589, PMID   9392600
  17. ↑ Labuda M, Kozuch O, Zuffová E, Elecková E, Hails RS, Nuttall PA (1997), "Tick-borne encephalitis virus transmission between ticks cofeeding on specific immune natural rodent hosts", Virology , 235 (1): 138–43, doi: 10.1006/viro.1997.8622 , PMID   9300045
  18. ↑ Jones LD, Hodgson E, Nuttall PA (1989), "Enhancement of virus transmission by tick salivary glands", Journal of General Virology , 70 (7): 1895–98, doi: 10.1099/0022-1317-70-7-1895 , PMID   2544668
  19. ↑ Sonenshine DE; Roe RM, eds. (2013), Biology of Ticks, Volume 2, Oxford University Press
  20. 1 2 3 4 Willadsen P (2004), "Anti-tick vaccines" (PDF), Parasitology , 129: S367-87, doi:10.1017/s0031182003004657, PMID   15938519, S2CID   40368916
  21. ↑ Wang H, Paesen GC, Nuttall PA, Barbour AG (1998), "Male ticks help their mates to feed", Nature , 391 (6669): 753–54, Bibcode:1998Natur.391..753W, doi:10.1038/35773, PMID   9486641, S2CID   4398008
  22. 1 2 3 4 Macilwain C (2006), "Ticking the right boxes", Nature , 439 (7076): 533, Bibcode:2006Natur.439..533M, doi: 10.1038/439533a , PMID   16452953, S2CID   4425421
  23. ↑ Paesen GC, Adams PL, Harlos K, Nuttall PA, Stuart DI (1999), "Tick histamine-binding proteins: Isolation, cloning, and three-dimensional structure", Molecular Cell , 3 (5): 661–71, doi: 10.1016/s1097-2765(00)80359-7 , PMID   10360182
  24. ↑ Koh CY, Kazimirova M, Trimnell A, Takac P, Labuda M, Nuttall PA, Kini RM (2007), "Variegin, a novel fast and tight binding thrombin inhibitor from the tropical bont tick", Journal of Biological Chemistry , 282 (40): 29101–13, doi: 10.1074/jbc.m705600200 , PMID   17684009
  25. ↑ "Drugs designed by nature could prevent heart attacks and blood clots", Centre for Ecology & Hydrology website, Natural Environment Research Council , retrieved 18 March 2015
  26. ↑ Labuda M, Trimnell AR, Licková M, Kazimírová M, Davies GM, Lissina O, Hails RS, Nuttall PA (2006), "An anti-vector vaccine protects against a lethal vector-borne pathogen", PLOS Pathogens , 2 (4): e27, doi: 10.1371/journal.ppat.0020027 , PMC   1424664 , PMID   16604154
  27. ↑ "New Year Honours List — United Kingdom", The London Gazette , 55710: 15, 31 December 1999
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