Peter Simmonds

Royal Infirmary of Edinburgh, Edinburgh, SCT, United Kingdom

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Publications (5)24.81 Total impact

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    Article: Independent evolution of macrophage-tropism and increased charge between HIV-1 R5 envelopes present in brain and immune tissue.
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    ABSTRACT: Transmitted HIV-1 clade B or C R5 viruses have been reported to infect macrophages inefficiently, while other studies have described R5 viruses in late disease with either an enhanced macrophage-tropism or carrying envelopes with an increased positive charge and fitness. In contrast, our previous data suggested that viruses carrying non-macrophage-tropic R5 envelopes were still predominant in immune tissue of AIDS patients. To further investigate the tropism and charge of HIV-1 viruses in late disease, we evaluated the properties of HIV-1 envelopes amplified from immune and brain tissues of AIDS patients with neurological complications. Almost all envelopes amplified were R5. There was clear compartmentalization of envelope sequences for four of the five subjects. However, strong compartmentalization of macrophage-tropism in brain was observed even when brain and immune tissue envelope sequences were not segregated. R5 envelopes from immune tissue of four subjects carried a higher positive charge compared to brain envelopes. We also confirm a significant correlation between macrophage tropism and sensitivity to soluble CD4, a weak association with sensitivity to the CD4 binding site antibody, b12, but no clear relationship with maraviroc sensitivity. Our study shows that non-macrophage-tropic R5 envelopes carrying gp120s with an increased positive charge were predominant in immune tissue in late disease. However, highly macrophage-tropic variants with lower charged gp120s were nearly universal in the brain. These results are consistent with HIV-1 R5 envelopes evolving gp120s with an increased positive charge in immune tissue or sites outside the brain that likely reflect an adaptation for increased replication or fitness for CD4+ T-cells. Our data are consistent with the presence of powerful pressures in brain and in immune tissues selecting for R5 envelopes with very different properties; high macrophage-tropism, sCD4 sensitivity and low positive charge in brain and non-macrophage-tropism, sCD4 resistance and high positive charge in immune tissue.
    Retrovirology 03/2012; 9:20. · 6.47 Impact Factor
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    Article: Origin and fate of A/H1N1 influenza in Scotland during 2009.
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    ABSTRACT: The spread of influenza has usually been described by a 'density' model, where the largest centres of population drive the epidemic within a country. An alternative model emphasizing the role of air travel has recently been developed. We have examined the relative importance of the two in the context of the 2009 H1N1 influenza epidemic in Scotland. We obtained genome sequences of 70 strains representative of the geographical and temporal distribution of H1N1 influenza during the summer and winter phases of the pandemic in 2009. We analysed these strains, together with another 128 from the rest of the UK and 292 globally distributed strains, using maximum-likelihood phylogenetic and bayesian phylogeographical methods. This revealed strikingly different epidemic patterns within Scotland in the early and late parts of 2009. The summer epidemic in Scotland was characterized by multiple independent introductions from both international and other UK sources, followed by major local expansion of a single clade that probably originated in Birmingham. The winter phase, in contrast, was more diverse genetically, with several clades of similar size in different locations, some of which had no particularly close phylogenetic affinity to strains sampled from either Scotland or England. Overall there was evidence to support both models, with significant links demonstrated between North American sequences and those from England, and between England and East Asia, indicating that major air-travel routes played an important role in the pattern of spread of the pandemic, both within the UK and globally.
    Journal of General Virology 02/2012; 93(Pt 6):1253-60. · 3.36 Impact Factor
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    Article: High seroprevalence of enterovirus infections in apes and old world monkeys.
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    ABSTRACT: To estimate population exposure of apes and Old World monkeys in Africa to enteroviruses (EVs), we conducted a seroepidemiologic study of serotype-specific neutralizing antibodies against 3 EV types. Detection of species A, B, and D EVs infecting wild chimpanzees demonstrates their potential widespread circulation in primates.
    Emerging Infectious Diseases 02/2012; 18(2):283-6. · 6.79 Impact Factor
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    Article: Species association of hepatitis B virus (HBV) in non-human apes; evidence for recombination between gorilla and chimpanzee variants.
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    ABSTRACT: Hepatitis B virus (HBV) infections are widely distributed in humans, infecting approximately one third of the world's population. HBV variants have also been detected and genetically characterised from Old World apes; Gorilla gorilla (gorilla), Pan troglodytes (chimpanzee), Pongo pygmaeus (orang-utan), Nomascus nastusus and Hylobates pileatus (gibbons) and from the New World monkey, Lagothrix lagotricha (woolly monkey). To investigate species-specificity and potential for cross species transmission of HBV between sympatric species of apes (such as gorillas and chimpanzees in Central Africa) or between humans and chimpanzees or gorillas, variants of HBV infecting captive wild-born non-human primates were genetically characterised. 9 of 62 chimpanzees (11.3%) and two from 11 gorillas (18%) were HBV-infected (15% combined frequency), while other Old world monkey species were negative. Complete genome sequences were obtained from six of the infected chimpanzee and both gorillas; those from P. t .ellioti grouped with previously characterised variants from this subspecies. However, variants recovered from P. t. troglodytes HBV variants also grouped within this clade, indicative of transmission between sub-species, forming a paraphyletic clade. The two gorilla viruses were phylogenetically distinct from chimpanzee and human variants although one showed evidence for a recombination event with a P.t.e.-derived HBV variant in the partial X and core gene region. Both of these observations provide evidence for circulation of HBV between different species and sub-species of non-human primates, a conclusion that differs from the hypothesis if of strict host specificity of HBV genotypes.
    PLoS ONE 01/2012; 7(3):e33430. · 4.09 Impact Factor
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    Article: Novel positive-sense, single-stranded RNA (+ssRNA) virus with di-cistronic genome from intestinal content of freshwater carp (Cyprinus carpio).
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    ABSTRACT: A novel positive-sense, single-stranded RNA (+ssRNA) virus (Halastavi árva RNA virus, HalV; JN000306) with di-cistronic genome organization was serendipitously identified in intestinal contents of freshwater carps (Cyprinus carpio) fished by line-fishing from fishpond "Lőrinte halastó" located in Veszprém County, Hungary. The complete nucleotide (nt) sequence of the genomic RNA is 9565 nt in length and contains two long--non-in-frame--open reading frames (ORFs), which are separated by an intergenic region. The ORF1 (replicase) is preceded by an untranslated sequence of 827 nt, while an untranslated region of 139 nt follows the ORF2 (capsid proteins). The deduced amino acid (aa) sequences of the ORFs showed only low (less than 32%) and partial similarity to the non-structural (2C-like helicase, 3C-like cystein protease and 3D-like RNA dependent RNA polymerase) and structural proteins (VP2/VP4/VP3) of virus families in Picornavirales especially to members of the viruses with dicistronic genome. Halastavi árva RNA virus is present in intestinal contents of omnivorous freshwater carps but the origin and the host species of this virus remains unknown. The unique viral sequence and the actual position indicate that Halastavi árva RNA virus seems to be the first member of a new di-cistronic ssRNA virus. Further studies are required to investigate the specific host species (and spectrum), ecology and role of Halastavi árva RNA virus in the nature.
    PLoS ONE 01/2011; 6(12):e29145. · 4.09 Impact Factor