Dr Ravinder Kanda
Senior Lecturer in Evolutionary Genomics
School of Biological and Medical Sciences
Research
Groups
Publications
slide 1 of 6
Journal articles
-
Kanda RK, Coulson T, 'The effect of life history on retroviral genome invasions'
PLoS ONE 10 (2) (2015) pp.1-17
ISSN: 1932-6203AbstractEndogenous retroviruses (ERV), or the remnants of past retroviral infections that are no longer active, are found in the genomes of most vertebrates, typically constituting approximately 10% of the genome. In some vertebrates, particularly in shorter-lived species like rodents, it is not unusual to find active endogenous retroviruses. In longer-lived species, including humans where substantial effort has been invested in searching for active ERVs, it is unusual to find them; to date none have been found in humans. Presumably the chance of detecting an active ERV infection is a function of the length of an ERV epidemic. Intuitively, given that ERVs or signatures of past ERV infections are passed from parents to offspring, we might expect to detect more active ERVs in species with longer generation times, as it should take more years for an infection to run its course in longer than in shorter lived species. This means the observation of more active ERV infections in shorter compared to longer-lived species is paradoxical. We explore this paradox using a modeling approach to investigate factors that influence ERV epidemic length. Our simple epidemiological model may explain why we find evidence of active ERV infections in shorter rather than longer-lived species.Published here Open Access on RADAR -
Lee A, Huntley D, Aiewsakun P, Kanda RK, Lynn C, Tristem M, 'Novel Denisovan and Neanderthal Retroviruses'
Journal of Virology 88 (21) (2014) pp.12907-12909
ISSN: 0022-538XAbstractFollowing the recent availability of high-coverage genomes for Denisovan and Neanderthal hominids, we conducted a screen for endogenized retroviruses, identifying six novel, previously unreported HERV-K(HML2) elements (HERV-K is human endogenous retrovirus K). These elements are absent from the human genome (hg38) and appear to be unique to archaic hominids. These findings provide further evidence supporting the recent activity of the HERV-K(HML2) group, which has been implicated in human disease. They will also provide insights into the evolution of archaic hominids.Published here Open Access on RADAR -
Jones M, Dry IR, Frampton D, Singh M, Kanda RK, Yee MB, Kellam P, Hollinshead M, Kinchington PR, O'Toole EA, Breuer J, 'RNA-seq analysis of host and viral gene expression highlights interaction between varicella zoster virus and keratinocyte differentiation'
PLoS Pathogens 10 (1) (2014) pp.e1003896-
ISSN: 1553-7366 eISSN: 1533-7374AbstractVaricella zoster virus (VZV) is the etiological agent of chickenpox and shingles, diseases characterized by epidermal skin blistering. Using a calcium-induced keratinocyte differentiation model we investigated the interaction between epidermal differentiation and VZV infection. RNA-seq analysis showed that VZV infection has a profound effect on differentiating keratinocytes, altering the normal process of epidermal gene expression to generate a signature that resembles patterns of gene expression seen in both heritable and acquired skin-blistering disorders. Further investigation by real-time PCR, protein analysis and electron microscopy revealed that VZV specifically reduced expression of specific suprabasal cytokeratins and desmosomal proteins, leading to disruption of epidermal structure and function. These changes were accompanied by an upregulation of kallikreins and serine proteases. Taken together VZV infection promotes blistering and desquamation of the epidermis, both of which are necessary to the viral spread and pathogenesis. At the same time, analysis of the viral transcriptome provided evidence that VZV gene expression was significantly increased following calcium treatment of keratinocytes. Using reporter viruses and immunohistochemistry we confirmed that VZV gene and protein expression in skin is linked with cellular differentiation. These studies highlight the intimate host-pathogen interaction following VZV infection of skin and provide insight into the mechanisms by which VZV remodels the epidermal environment to promote its own replication and spread.Published here -
Kanda R, Tristem M, Coulson T, 'Exploring the effects of immunity and life history on the dynamics of an endogenous retrovirus'
Philosophical Transactions of the Royal Society B: Biological Sciences 368 (1626) (2013)
ISSN: 0962-8436 eISSN: 1471-2970AbstractMammalian DNA is littered with the signatures of past retroviral infections. For example, at least 8% of the human genome can be attributed to endogenous retroviruses (ERVs). We take a single-locus approach to develop a simple susceptible–infected–recovered model to investigate the circumstances under which a disease-causing retrovirus can become incorporated into the host genome and spread through the host population if it were to confer an immunological advantage. In the absence of any fitness benefit provided by the long terminal repeat (LTR), we conclude that signatures of ERVs are likely to go to fixation within a population when the probability of evolving cellular/humoral immunity to a related exogenous version of the virus is extremely small. We extend this model to examine whether changing the speed of the host life history influences the likelihood that an exogenous retrovirus will incorporate and spread to fixation. Our results reveal the parameter space under which incorporation of exogenous retroviruses into a host genome may be beneficial to the host. In our final model, we find that the likelihood of an LTR reaching fixation in a host population is not strongly affected by host life history.Published here -
Depledge DP, Palser AL, Watson SJ, Lai I, Gray ER, Grant P, Kanda RK, Leproust E, Kellam P, Breuer J, 'Correction: Specific capture and whole-genome sequencing of viruses from clinical samples'
PLoS ONE 7 (1) (2011)
ISSN: 1932-6203AbstractThere was an error in the accession number in Materials and Methods. EBV and KSHV dataset can be found under the Study Accession number: ERP001026. Individual Sample Accessions are as follows: 1208_JSC1_SN_KS - ERS074823 1212_HBL6_SN_KS - ERS074824 1210_JSC1_SN_EB - ERS074825 1215_HBL6_SN_EB - ERS074833Published here -
Depledge DP, Palser AL, Watson SJ, Lai IY, Gray ER, Grant P, Kanda RK, Leproust E, Kellam P, Breuer J, 'Specific capture and whole-genome sequencing of viruses from clinical samples'
PLoS ONE 6 (11) (2011) pp.e27805-
ISSN: 1932-6203AbstractWhole genome sequencing of viruses directly from clinical samples is integral for understanding the genetics of host-virus interactions. Here, we report the use of sample sparing target enrichment (by hybridisation) for viral nucleic acid separation and deep-sequencing of herpesvirus genomes directly from a range of clinical samples including saliva, blood, virus vesicles, cerebrospinal fluid, and tumour cell lines. We demonstrate the effectiveness of the method by deep-sequencing 13 highly cell-associated human herpesvirus genomes and generating full length genome alignments at high read depth. Moreover, we show the specificity of the method enables the study of viral population structures and their diversity within a range of clinical samples types.Published here -
Kanda R, Quinlivan M, Gershon A, Nichols R, Breuer J, 'Population diversity in batches of the varicella Oka vaccine'
Vaccine 29 (17) (2011) pp.3293-3298
AbstractThe Oka vaccine is a live attenuated vaccine for the prevention of varicella. Although the vaccine differs from the progenitor virus by over 40 mutations, only three of these are fixed, the rest being a mixture of the wildtype and the vaccine allele. To examine the extent of this variability between two of the three commercially available vaccine preparations, we analysed the vaccine/wildtype allele frequencies present at fifteen vaccine loci in five preparations each from two different manufacturers of the vOka vaccine. Our results suggest that differences in manufacturing processes between the two companies have resulted in significant variation in the frequencies of the vaccine/wildtype alleles in their vaccines. Yet despite these differences, the allele frequencies in the vaccines from the two companies are strongly correlated. We discuss the significance of these findings and the role of evolutionary processes that influence the production of this live attenuated vaccine.Published here -
Bussell JJ, Pearson NM, Kanda R, Filatov DA, Lahn BT, 'Human polymorphism and human--chimpanzee divergence in pseudoautosomal region correlate with local recombination rate'
Gene 368 (2006) pp.94-100
ISSN: 0378-1119 eISSN: 1879-0038AbstractPrevious studies have shown widespread correlation between nucleotide polymorphism and recombination rate, but the cause of this correlation is unresolved. One explanation is that recombination is associated with point mutations, potentially through mutagenic effects of meiotic crossover. This hypothesis predicts that regions of frequent recombination should show both elevated nucleotide diversity within a species and increased nucleotide divergence between species. Here we tested this hypothesis by studying the human short-arm pseudoautosomal region (PAR1), which recombines between X and Y chromosomes in men at a rate ∼20 times the genome average. We sequenced dispersed intronic loci within PAR1 in a panel of humans and in the chimpanzee and directly measured sequence variation and recombination rate from these data. In line with previous reports, we saw a correlation between human polymorphism level and local recombination rate. Moreover, we also found a highly significant correlation between human–chimpanzee divergence and recombination rate. These results are consistent with the hypothesis that recombination is associated with point mutations, possibly because recombination is mutagenic.Published here
Other publications
-
Kanda R, 'Genomic diversity in humans', (2003)