| 1. |
- Barnes, Ian, et al.
(författare)
-
Ancient urbanization predicts genetic resistance to tuberculosis
- 2011
-
Ingår i: Evolution. - : Wiley. - 0014-3820 .- 1558-5646. ; 65:3, s. 842-848
-
Tidskriftsartikel (refereegranskat)abstract
- A link between urban living and disease is seen in recent and historical records, but the presence of this association in prehistory has been difficult to assess. If the transition to urban living does result in an increase in disease-based mortality, we might expect to see evidence of increased disease resistance in longer-term urbanized populations, as the result of natural selection. To test this, we determined the frequency of an allele (SLC11A1 1729 + 55del4) associated with natural resistance to intracellular pathogens such as tuberculosis and leprosy. We found a highly significantly correlation with duration of urban settlement-populations with a long history of living in towns are better adapted to resisting these infections. This correlation remains strong when we correct for autocorrelation in allele frequencies due to shared population history. Our results therefore support the interpretation that infectious disease loads became an increasingly important cause of human mortality after the advent of urbanization, highlighting the importance of population density in determining human health and the genetic structure of human populations.
|
|
| 2. |
- Fiddaman, Steven R., et al.
(författare)
-
Ancient chicken remains reveal the origins of virulence in Marek's disease virus
- 2023
-
Ingår i: Science (New York, N.Y.). - 1095-9203. ; 382:6676, s. 1276-1281
-
Tidskriftsartikel (refereegranskat)abstract
- The pronounced growth in livestock populations since the 1950s has altered the epidemiological and evolutionary trajectory of their associated pathogens. For example, Marek's disease virus (MDV), which causes lymphoid tumors in chickens, has experienced a marked increase in virulence over the past century. Today, MDV infections kill >90% of unvaccinated birds, and controlling it costs more than US$1 billion annually. By sequencing MDV genomes derived from archeological chickens, we demonstrate that it has been circulating for at least 1000 years. We functionally tested the Meq oncogene, one of 49 viral genes positively selected in modern strains, demonstrating that ancient MDV was likely incapable of driving tumor formation. Our results demonstrate the power of ancient DNA approaches to trace the molecular basis of virulence in economically relevant pathogens.
|
|
| 3. |
- Hassan, Amin S., et al.
(författare)
-
Defining HIV-1 transmission clusters based on sequence data : a systematic review and perspectives
- 2017
-
Ingår i: AIDS. - 0269-9370. ; 31:9, s. 1211-1222
-
Forskningsöversikt (refereegranskat)abstract
- Understanding HIV-1 transmission dynamics is relevant to both screening and intervention strategies of HIV-1 infection. Commonly, HIV-1 transmission chains are determined based on sequence similarity assessed either directly from a sequence alignment or by inferring a phylogenetic tree. This review is aimed at both nonexperts interested in understanding and interpreting studies of HIV-1 transmission, and experts interested in finding the most appropriate cluster definition for a specific dataset and research question. We start by introducing the concepts and methodologies of how HIV-1 transmission clusters usually have been defined. We then present the results of a systematic review of 105 HIV-1 molecular epidemiology studies summarising the most popular methods and definitions in the literature. Finally, we offer our perspectives on how HIV-1 transmission clusters can be defined and provide some guidance based on examples from real life datasets.
|
|
| 4. |
- Volz, Erik, et al.
(författare)
-
Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity
- 2021
-
Ingår i: Cell. - : Elsevier BV. - 1097-4172 .- 0092-8674. ; 184:1, s. 11-75
-
Tidskriftsartikel (refereegranskat)abstract
- Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant.
|
|
| 5. |
- Wille, Michelle, et al.
(författare)
-
Evolutionary features of a prolific subtype of avian influenza A virus in European waterfowl
- 2022
-
Ingår i: Virus Evolution. - : Oxford University Press. - 2057-1577. ; 8:2
-
Tidskriftsartikel (refereegranskat)abstract
- Avian influenza A virus (AIV) is ubiquitous in waterfowl and is detected annually at high prevalence in waterfowl during the Northern Hemisphere autumn. Some AIV subtypes are globally common in waterfowl, such as H3N8, H4N6, and H6N2, and are detected in the same populations at a high frequency, annually. In order to investigate genetic features associated to the long-term maintenance of common subtypes in migratory ducks, we sequenced 248 H4 viruses isolated across 8 years (2002-9) from mallards (Anas platyrhynchos) sampled in southeast Sweden. Phylogenetic analyses showed that both H4 and N6 sequences fell into three distinct lineages, structured by year of isolation. Specifically, across the 8 years of the study, we observed lineage replacement, whereby a different HA lineage circulated in the population each year. Analysis of deduced amino acid sequences of the HA lineages illustrated key differences in regions of the globular head of hemagglutinin that overlap with established antigenic sites in homologous hemagglutinin H3, suggesting the possibility of antigenic differences among these HA lineages. Beyond HA, lineage replacement was common to all segments, such that novel genome constellations were detected across years. A dominant genome constellation would rapidly amplify in the duck population, followed by unlinking of gene segments as a result of reassortment within 2-3 weeks following introduction. These data help reveal the evolutionary dynamics exhibited by AIV on both annual and decadal scales in an important reservoir host.
|
|
| 6. |
- Wille, Michelle, et al.
(författare)
-
Where do all the subtypes go? : Temporal dynamics of H8-H12 influenza A viruses in waterfowl
- 2018
-
Ingår i: Virus Evolution. - : Oxford University Press. - 2057-1577. ; 4:2
-
Tidskriftsartikel (refereegranskat)abstract
- Influenza A virus (IAV) is ubiquitous in waterfowl. In the northern hemisphere IAV prevalence is highest during the autumn and coincides with a peak in viral subtype diversity. Although haemagglutinin subtypes H1-H12 are associated with waterfowl hosts, subtypes H8-H12 are detected very infrequently. To better understand the role of waterfowl in the maintenance of these rare subtypes, we sequenced H8-H12 viruses isolated from Mallards (Anas platyrhynchos) from 2002 to 2009. These rare viruses exhibited varying ecological and phylodynamic features. The Eurasian clades of H8 and H12 phylogenies were dominated by waterfowl sequences; mostly viruses sequenced in this study. H11, once believed to be a subtype that infected charadriiformes (shorebirds), exhibited patterns more typical of common virus subtypes. Finally, subtypes H9 and H10, which have maintained lineages in poultry, showed markedly different patterns: H10 was associated with all possible NA subtypes and this drove HA lineage diversity within years. Rare viruses belonging to subtypes H8-H12 were highly reassorted, indicating that these rare subtypes are part of the broader IAV pool. Our results suggest that waterfowl play a role in the maintenance of these rare subtypes, but we recommend additional sampling of non-traditional hosts to better understand the reservoirs of these rare viruses.
|
|
| 7. |
- Özkaya Sahin, Gülsen, et al.
(författare)
-
Generation of neutralizing antibodies and divergence of SIVmac239 in cynomolgus macaques following short-term early antiretroviral therapy.
- 2010
-
Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 6:9
-
Tidskriftsartikel (refereegranskat)abstract
- Neutralizing antibodies (NAb) able to react to heterologous viruses are generated during natural HIV-1 infection in some individuals. Further knowledge is required in order to understand the factors contributing to induction of cross-reactive NAb responses. Here a well-established model of experimental pathogenic infection in cynomolgus macaques, which reproduces long-lasting HIV-1 infection, was used to study the NAb response as well as the viral evolution of the highly neutralization-resistant SIVmac239. Twelve animals were infected intravenously with SIVmac239. Antiretroviral therapy (ART) was initiated ten days post-inoculation and administered daily for four months. Viral load, CD4(+) T-cell counts, total IgG levels, and breadth as well as strength of NAb in plasma were compared simultaneously over 14 months. In addition, envs from plasma samples were sequenced at three time points in all animals in order to assess viral evolution. We report here that seven of the 12 animals controlled viremia to below 10(4) copies/ml of plasma after discontinuation of ART and that this control was associated with a low level of evolutionary divergence. Macaques that controlled viral load developed broader NAb responses early on. Furthermore, escape mutations, such as V67M and R751G, were identified in virus sequenced from all animals with uncontrolled viremia. Bayesian estimation of ancestral population genetic diversity (PGD) showed an increase in this value in non-controlling or transient-controlling animals during the first 5.5 months of infection, in contrast to virus-controlling animals. Similarly, non- or transient controllers displayed more positively-selected amino-acid substitutions. An early increase in PGD, resulting in the generation of positively-selected amino-acid substitutions, greater divergence and relative high viral load after ART withdrawal, may have contributed to the generation of potent NAb in several animals after SIVmac239 infection. However, early broad NAb responses correlated with relatively preserved CD4(+) T-cell numbers, low viral load and limited viral divergence.
|
|
