Dr Carol Leitch

Affiliate (School of Infection & Immunity)

MRC-University of Glasgow Centre for Virus Research, Sir Michael Stoker Building, Garscube Campus, 464 Bearsden Road, G61 1QH

Research interests

Member of the Mclauchlan Group.

RNA Viral Evolution, Diversity and Transmission

My main research interest is RNA virus evolution, diversity and transmission dynamics. Due to rapid replication rates combined with the error-prone nature of RNA polymerases, RNA virus infections are comprised of a population of closely-related but genetically non-identical virions termed a quasispecies. The huge genetic diversity contained within a quasispecies allows rapid adaptation to environmental changes so that they can, for instance, develop resistance to antiviral compounds and escape the host immune defences.

Hepatitis C Virus

Currently my research is focused on Hepatitis C virus (HCV). This RNA virus is a major cause of liver disease and infects around 3% of the world’s population. Seven HCV genotypes (1-7) have been identified and their global distribution varies, as does the overall prevalence of HCV. In the UK, genotypes 1a and 3a are the most common. Although up to 50% of infected individuals clear the virus spontaneously, many go on to develop a chronic disease which can result in liver cirrhosis or hepatocellular carcinoma.

There is no vaccine against HCV and the recently developed direct acting antiviral (DAA) drugs are extremely expensive. In addition drug resistance frequently requires only a single nucleotide change within the HCV genome. Due to the HCV quasispecies and its inherent genetic diversity, resistant strains may be present within an infected individual before treatment commences and expansion of a resistant population can therefore occur rapidly.

Research Interests

My research is currently focussed on viral transmission dynamics and diversity at scales ranging from the population level to the cellular level.

‌At the population level we are currently studying HCV circulation between people who inject drugs in order to identify hotspots of transmission, key regions driving viral spread. By targeting intervention strategies such as “treatment as prevention” initiatives to these areas we can maximise their impact. Using Bayesian inference methods, we reconstructed the global origin and local transmission of HCV in Scotland. We determined that HCV was introduced into Scotland in the 1940s concomitant with its worldwide dispersal. Cluster-specific transmission hubs were identified in Glasgow, the key Scottish city implicated in driving HCV dissemination (McNaughton et al, J Virol 2015, 89:11223). We are now investigating the spread of HCV in the rest of the UK.

‌To download a movie showing HCV spread within Scotland from McNaughton et al, J Virol 2015, 89:11223, please see here: HCV spread Scotland video.

I am also interested in studying viral diversity and evolution at the cellular level. As cells form discrete compartments in which viruses can replicate separately, it is likely that evolution in individual cells occurs independently. This is of particular interest with regards to non-lytic RNA viruses such as HCV that cause chronic infections in long-lived cells e.g. hepatocytes. Research within the group has characterised the diversity of HCV replicon quasispecies and the divergent evolution in individual Huh7 cells (Leitch and McLauchlan, J. Virol. 2013, 87:12648). Currently we are examining the cellular HCV quasispecies diversity in patient-derived samples and the effect on the host immune response.

Other research interests

This includes HCV co-infections, the emergence of antiviral escape mutants and HCV-associated disease progression correlates. We are also interested in hepatitis B virus and Dengue virus.

Lab Members

Anna McNaughton (PhD student)

Collaborators

Rory Gunson (West of Scotland Specialist Virology Centre)
Kate Templeton (Royal Infirmary of Edinburgh)
Philip Meuleman (University of Ghent, Belgium)
David Goldberg and Sharon Hutchison (Health Protection Scotland)

Publications

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Number of items: 40.

2021

Da Silva Filipe, A. et al. (2021) Genomic epidemiology reveals multiple introductions of SARS-CoV-2 from mainland Europe into Scotland. Nature Microbiology, 6(1), pp. 112-122. (doi: 10.1038/s41564-020-00838-z) (PMID:33349681)

2019

Xu, R. et al. (2019) HCV genotype 6 prevalence, spontaneous clearance and diversity amongst elderly members of the Li ethnic minority in Baisha County, China. Journal of Viral Hepatitis, 26(5), pp. 529-540. (doi: 10.1111/jvh.13062) (PMID:30629794)

2018

Nickbakhsh, S. , McLauchlan, J. and Leitch, E. C. M. (2018) Evaluating “treatment as prevention” on the road to hepatitis C virus elimination. Annals of Blood, 3, 44. (doi: 10.21037/aob.2018.10.05)

McNaughton, A.L., Sreenu, V.B. , Wilkie, G., Gunson, R., Templeton, K. and Leitch, E.C.M. (2018) Prevalence of mixed genotype hepatitis C virus infections in the UK as determined by genotype‐specific PCR and deep sequencing. Journal of Viral Hepatitis, 25(5), pp. 524-534. (doi: 10.1111/jvh.12849) (PMID:29274184) (PMCID:PMC5947153)

2015

McNaughton, A. L., Cameron, I. D., Wignall-Fleming, E. B., Biek, R. , McLauchlan, J. , Gunson, R. N., Templeton, K., Tan, H. M.-L. and McWilliam Leitch, E. C. (2015) Spatiotemporal reconstruction of the introduction of hepatitis C virus into Scotland and its subsequent regional transmission. Journal of Virology, 89(22), pp. 11223-11232. (doi: 10.1128/JVI.02106-15) (PMID:26311892) (PMCID:PMC4645645)

2014

Harvala, H., Calvert, J., Van Nguyen, D., Clasper, L., Gadsby, N., Molyneaux, P., Templeton, K., McWilliams Leitch, C. and Simmonds, P. (2014) Comparison of diagnostic clinical samples and environmental sampling for enterovirus and parechovirus surveillance in Scotland, 2010 to 2012. Eurosurveillance, 19(15), p. 20772. (doi: 10.2807/1560-7917.ES2014.19.15.20772) (PMID:24762664)

McNaughton, A.L., Thomson, E.C. , Templeton, K., Gunson, R.N. and McWilliam Leitch, E.C. (2014) Mixed genotype hepatitis C infections and implications for treatment. Hepatology, 59(3), p. 1209. (doi: 10.1002/hep.26544) (PMID:23744801) (PMCID:PMC4296219)

Reichardt, N., Duncan, S. H., Young, P., Belenguer, A., McWilliam Leitch, C., Scott, K. P., Flint, H. J. and Louis, P. (2014) Phylogenetic distribution of three pathways for propionate production within the human gut microbiota. ISME Journal, 8(6), pp. 1323-1335. (doi: 10.1038/ismej.2014.14) (PMID:24553467) (PMCID:PMC4030238)

2013

McWilliam Leitch, E. C. and McLauchlan, J. (2013) Determining the cellular diversity of hepatitis C virus quasispecies by single-cell viral sequencing. Journal of Virology, 87(23), pp. 12648-12655. (doi: 10.1128/JVI.01602-13) (PMID:24049174) (PMCID:PMC3838117)

Leggewie, M., Sreenu, V. B. , Abdelrahman, T., Leitch, E. C., Wilkie, G., Klymenko, T., Muir, D., Thursz, M., Main, J. and Thomson, E.C. (2013) Natural NS3 resistance polymorphisms occur frequently prior to treatment in HIV-positive patients with acute hepatitis C. AIDS, 27(15), pp. 2485-2488. (doi: 10.1097/QAD.0b013e328363b1f9) (PMID:23770494)

2012

McLeish, N.J. et al. (2012) Development and assay of RNA transcripts of enterovirus species A to D, rhinovirus species a to C, and human parechovirus: assessment of assay sensitivity and specificity of real-time screening and typing methods. Journal of Clinical Microbiology, 50(9), pp. 2910-2917.

McWilliam Leitch, E.C. et al. (2012) The association of recombination events in the founding and emergence of subgenogroup evolutionary lineages of human enterovirus 71. Journal of Virology, 86(5), pp. 2676-2685. (doi: 10.1128/JVI.06065-11)

2011

Bennett, S., Harvala, H., Witteveldt, J., McWilliam Leitch, E.C., McLeish, N., Templeton, K., Gunson, R., Carman, W.F. and Simmonds, P. (2011) Rapid simultaneous detection of enterovirus and parechovirus RNAs in clinical samples by one-step real-time reverse transcription-PCR assay. Journal of Clinical Microbiology, 49(7), pp. 2620-2624.

Harvala, H., McLeish, N., Kondracka, J., McIntyre, C. L., McWilliam Leitch, E. C., Templeton, K. and Simmonds, P. (2011) Comparison of human parechovirus and enterovirus detection frequencies in cerebrospinal fluid samples collected over a 5-year period in Edinburgh: HPeV type 3 identified as the most common picornavirus type. Journal of Medical Virology, 83(5), pp. 889-896. (doi: 10.1002/jmv.22023) (PMID:21412796)

2010

McIntyre, C.L., McWilliam-Leitch, E.C., Savolainen-Kopra, C., Hovi, T. and Simmonds, P. (2010) Analysis of genetic diversity and sites of recombination in human rhinovirus species C. Journal of Virology, 84(19), pp. 10297-10310. (doi: 10.1128/JVI.00962-10)

McWilliam Leitch, E.C. et al. (2010) Evolutionary dynamics and temporal/geographical correlates of recombination in the human enterovirus echovirus types 9, 11, and 30. Journal of Virology, 84(18), pp. 9292-9300. (doi: 10.1128/JVI.00783-10)

Calvert, J. et al. (2010) Recombination dynamics of human parechoviruses: investigation of type-specific differences in frequency and epidemiological correlates. Journal of General Virology, 91(5), pp. 1229-1238. (doi: 10.1099/vir.0.018747-0)

2009

Gaunt, E., McWilliam-Leitch, E.C., Templeton, K. and Simmonds, P. (2009) Incidence, molecular epidemiology and clinical presentations of human metapneumovirus; assessment of its importance as a diagnostic screening target. Journal of Clinical Virology, 46(4), pp. 318-324. (doi: 10.1016/j.jcv.2009.09.016)

Wisdom, A., McWilliam Leitch, E.C., Gaunt, E., Harvala, H. and Simmonds, P. (2009) Screening Respiratory Samples for Detection of Human Rhinoviruses (HRVs) and enteroviruses: comprehensive VP4-VP2 typing reveals high incidence and genetic diversity of HRV species C. Journal of Clinical Microbiology, 47(12), pp. 3958-3967.

Harvala, H., Robertson, I., Chieochansin, T., McWilliam Leitch, E.C., Templeton, K. and Simmonds, P. (2009) Specific association of human parechovirus type 3 with sepsis and fever in young infants, as identified by direct typing of cerebrospinal fluid samples. Journal of Infectious Diseases, 199(12), pp. 1753-1760. (doi: 10.1086/599094)

McWilliam Leitch, E.C. et al. (2009) Transmission networks and population turnover of echovirus 30. Journal of Virology, 83(5), pp. 2109-2118. (doi: 10.1128/JVI.02109-08)

McWilliam Leitch, E.C., Harvala, H., Robertson, I., Ubillos, I., Templeton, K. and Simmonds, P. (2009) Direct identification of human enterovirus serotypes in cerebrospinal fluid by amplification and sequencing of the VP1 region. Journal of Clinical Virology, 44(2), pp. 119-124. (doi: 10.1016/j.jcv.2008.11.015)

Wisdom, A., Kutkowska, A.E., McWilliam Leitch, E.C., Gaunt, E., Templeton, K., Harvala, H. and Simmonds, P. (2009) Genetics, recombination and clinical features of human rhinovirus species C (HRV-C) infections; interactions of HRV-C with other respiratory viruses. PLoS ONE, 4(12), e8518. (doi: 10.1371/journal.pone.0008518)

2008

Harvala, H., Robertson, I., McWilliam Leitch, E.C., Benschop, K., Wolthers, K.C., Templeton, K. and Simmonds, P. (2008) Epidemiology and clinical associations of human parechovirus respiratory infections. Journal of Clinical Microbiology, 46(10), pp. 3446-3453. (doi: 10.1128/JCM.01207-08)

2007

Leitch, E. C. M., Walker, A. W., Duncan, S. H., Holtrop, G. and Flint, H. J. (2007) Selective colonization of insoluble substrates by human faecal bacteria. Environmental Microbiology, 9(3), pp. 667-679. (doi: 10.1111/j.1462-2920.2006.01186.x) (PMID:17298367)

2006

Flint, H. J., Leitch, E.C.M., Duncan, S. H., Walker, A. W., Patterson, A. J., Rincon, M. T., Scott, K. P. and Louis, P. (2006) Molecular approaches to the analysis of gastrointestinal microbial ecosystems. In: Perry, G.C. (ed.) Avian Gut Function in Health and Disease. Series: Poultry science symposium series (28). CABI: Cambridge, MA, pp. 107-123. ISBN 9781845931803 (doi: 10.1079/9781845931803.0107)

2005

Walker, A. W., Duncan, S. H., McWilliam Leitch, E. C., Child, M. W. and Flint, H. J. (2005) pH and peptide supply can radically alter bacterial populations and short-chain fatty acid ratios within microbial communities from the human colon. Applied and Environmental Microbiology, 71(7), pp. 3692-3700. (doi: 10.1128/AEM.71.7.3692-3700.2005) (PMID:16000778) (PMCID:PMC1169066)

2004

Duncan, S. H., McWilliam Leitch, E. C., Stanley, K. N., Richardson, A. J., Laven, R. A., Flint, H. J. and Stewart, C. S. (2004) Effects of esculin and esculetin on the survival of Escherichia coli O157 in human faecal slurries, continuous-flow simulations of the rumen and colon and in calves. British Journal of Nutrition, 91(5), pp. 749-755. (doi: 10.1079/BJN20041101) (PMID:15137927)

2002

McWilliam Leitch, E.C. and Stewart, C. S. (2002) Escherichia coli O157 and non-O157 isolates are more susceptible to L-lactate than to D-lactate. Applied and Environmental Microbiology, 68(9), pp. 4676-4678. (doi: 10.1128/AEM.68.9.4676-4678.2002) (PMID:12200331) (PMCID:PMC124064)

McWilliam Leitch, E.C. and Stewart, C.S. (2002) Susceptibility of Escherichia coli O157 and non-O157 isolates to lactate. Letters in Applied Microbiology, 35(3), pp. 176-180. (doi: 10.1046/j.1472-765X.2002.01164.x) (PMID:12180936)

2001

Leitch, E.C. and Willcox, M.D.P. (2001) Lactoferrin-induced reduction of vanB vancomycin resistance in enterococci. International Journal of Antimicrobial Agents, 18(4), pp. 399-402. (doi: 10.1016/S0924-8579(01)00415-0) (PMID:11691577)

McWilliam Leitch, E. C., Duncan, S. H., Stanley, K. N. and Stewart, C. S. (2001) Dietary effects on the microbiological safety of food. Proceedings of the Nutrition Society, 60(02), pp. 247-255. (doi: 10.1079/PNS200078)

Sweeney, D. F., Stapleton, F., Leitch, C., Taylor, J., Holden, B. A. and Willcox, M. D. P. (2001) Microbial colonization of soft contact lenses over time. Optometry and Vision Science, 78(2), pp. 100-105. (doi: 10.1097/00006324-200102000-00010) (PMID:11265924)

2000

Leitch, E.C. and March, J.B. (2000) Estimation of the titre of Mycoplasma mycoides subspecies mycoides SC vaccine strain T144 by pH and spectrophotometry. In: Bergonnier, D., Berthelot, X. and Frey, J. (eds.) Mycoplasmas of Ruminants: Pathogenicity, Diagnosis, Epidemiology and Molecular Genetics. European Communities: Luxembourg, pp. 147-150. ISBN 9789282906125