scholarly journals High resolution evolutionary analysis of within-host hepatitis C virus infection

2018 ◽  
Author(s):  
Jayna Raghwani ◽  
Chieh-Hsi Wu ◽  
Cynthia K. Y. Ho ◽  
Menno de Jong ◽  
Richard Molenkamp ◽  
...  

ABSTRACTDespite the breakthroughs in the treatment of HCV infection in recent years, we have a limited understanding of how virus diversity generated within individuals impacts the evolution and spread of HCV variants at the population scale. Addressing this gap will be important for building models for molecular epidemiology, which can identify main sources of disease transmission and evaluate the risks of drug-resistance mutations emerging and disseminating in a population. Here, we have undertaken a high-resolution analysis of HCV within-host evolution from four individuals co-infected with HIV. Specifically, we used long-read, deep-sequenced data of the full-length HCV envelope glycoprotein, longitudinally sampled from acute to chronic HCV infection to investigate the underlying viral evolutionary dynamics. In three individuals we found strong statistical support for population structure maintaining within-host HCV genetic diversity. Furthermore, we found significant variation in rates of molecular evolution among different regions of the HCV envelope region, both within and between individuals. Lastly, we report the first estimate of the within-host population genetic rate of recombination for HCV (0.28 x 10-7 recombinations per site per day; interquartile range: 0.13-1.05 x 10-7), which is two orders of magnitude lower than that estimated for HIV-1, and four orders of magnitude lower than the nucleotide substitution rate of the HCV envelope gene. Together, these observations indicate that population structure and strong genetic linkage shapes within-host HCV evolutionary dynamics. These results will guide the future investigation of potential HCV drug resistance adaptation during infection, and at the population scale.

2021 ◽  
Vol 9 (1) ◽  
pp. 147
Author(s):  
Ana Santos-Pereira ◽  
Carlos Magalhães ◽  
Pedro M. M. Araújo ◽  
Nuno S. Osório

The already enormous burden caused by Mycobacterium tuberculosis and Human Immunodeficiency Virus type 1 (HIV-1) alone is aggravated by co-infection. Despite obvious differences in the rate of evolution comparing these two human pathogens, genetic diversity plays an important role in the success of both. The extreme evolutionary dynamics of HIV-1 is in the basis of a robust capacity to evade immune responses, to generate drug-resistance and to diversify the population-level reservoir of M group viral subtypes. Compared to HIV-1 and other retroviruses, M. tuberculosis generates minute levels of genetic diversity within the host. However, emerging whole-genome sequencing data show that the M. tuberculosis complex contains at least nine human-adapted phylogenetic lineages. This level of genetic diversity results in differences in M. tuberculosis interactions with the host immune system, virulence and drug resistance propensity. In co-infected individuals, HIV-1 and M. tuberculosis are likely to co-colonize host cells. However, the evolutionary impact of the interaction between the host, the slowly evolving M. tuberculosis bacteria and the HIV-1 viral “mutant cloud” is poorly understood. These evolutionary dynamics, at the cellular niche of monocytes/macrophages, are also discussed and proposed as a relevant future research topic in the context of single-cell sequencing.


2009 ◽  
Vol 90 (12) ◽  
pp. 2877-2883 ◽  
Author(s):  
Giovanna Carpi ◽  
Luigi Bertolotti ◽  
Sergio Rosati ◽  
Annapaola Rizzoli

Tick-borne encephalitis (TBE) is a severe disease that has been endemic in north-east Italy since 1992. Over the past two decades, there has been an increase in the number of human cases reported in many European countries, including Italy. To assess the current TBE infection risk, questing ticks were collected from known TBE foci, as well as from a site in northern Italy where no human infections have been reported previously. A total of 1739 Ixodes ricinus (1485 nymphs and 254 adults) was collected and analysed for TBEV prevalence by a real-time RT-PCR targeting the 3′ untranslated region. Phylogenetic analyses of the partial envelope gene were conducted on two newly sequenced TBE virus (TBEV) strains and 28 previously published sequences to investigate the genealogical relationships of the circulating TBEV strains. These phylogenetic analyses confirmed a previous report that the European TBEV subtype is the only subtype circulating within the TBE foci in north-east Italy. Interestingly, nucleotide sequence analysis revealed a high degree of divergence (mean 2.54 %) between the TBEV strains recovered in the Italian province of Trento, despite the circulation of a single TBEV subtype. This elevated genetic variability within a single TBE focus may reflect local differences in the long-standing evolutionary dynamics of TBEV at this site relative to previously characterized sites, or more recent and continuous reintroduction of various TBEV strains.


Nature ◽  
2015 ◽  
Vol 519 (7542) ◽  
pp. 181-186 ◽  
Author(s):  
Sasha F. Levy ◽  
Jamie R. Blundell ◽  
Sandeep Venkataram ◽  
Dmitri A. Petrov ◽  
Daniel S. Fisher ◽  
...  

2004 ◽  
Vol 85 (6) ◽  
pp. 1479-1484
Author(s):  
Mary Poss ◽  
David C. Holley ◽  
Roman Biek ◽  
Harold Cox ◽  
John Gerdes

The virus population transmitted by a human immunodeficiency virus type 1 (HIV-1) infected individual undergoes restriction and subsequent diversification in the new host. However, in contrast to men, who have limited virus diversity at seroconversion, there is measurable diversity in viral envelope gene sequences in women infected with clade A HIV-1. In this study, virus sequence diversity in three unrelated, clade A infected women preceding and shortly after seroconversion was evaluated. It was demonstrated that there is measurable evolution of envelope gene sequences over this time interval. Furthermore, in each of the three individuals, amino acid substitutions arose at five or six positions in sequences derived at or shortly after seroconversion relative to sequences obtained from the seronegative sample. Presented here is a model of clade A gp120 to determine the location of substitutions that appeared as the virus population became established in three clade A HIV-1 infected women.


2020 ◽  
Author(s):  
Kimberly S. Vasquez ◽  
Lisa Willis ◽  
Nate Cira ◽  
Katharine M. Ng ◽  
Miguel F. Pedro ◽  
...  

SummaryDue to limitations on high-resolution strain tracking, selection dynamics during gut-microbiota colonization and transmission between hosts remain mostly mysterious. Here, we introduced hundreds of barcoded Escherichia coli strains into germ-free mice and quantified strain-level dynamics and metagenomic changes. Mutants involved in motility and utilization of abundant metabolites were reproducibly selected within days. Even with rapid selection, coprophagy enforced similar barcode distributions across co-housed mice. Whole-genome sequencing of hundreds of isolates quantified evolutionary dynamics and revealed linked alleles. A population-genetics model predicted substantial fitness advantages for certain mutants and that migration accounted for ~10% of the resident microbiota each day. Treatment with ciprofloxacin demonstrated the interplay between selection and transmission. While initial colonization was mostly uniform, in two mice a bottleneck reduced diversity and selected for ciprofloxacin resistance in the absence of drug. These findings highlight the interplay between environmental transmission and rapid, deterministic selection during evolution of the intestinal microbiota.


BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Gertrud Grilz-Seger ◽  
Thomas Druml ◽  
Markus Neuditschko ◽  
Max Dobretsberger ◽  
Michaela Horna ◽  
...  

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S54-S54
Author(s):  
Ron Dagan ◽  
Shalom Ben-Shimol ◽  
Rachel Benisty ◽  
Gili Regev-Yochay ◽  
Merav Ron ◽  
...  

Abstract Background IPD caused by Sp2 (non-PCV13 serotype) is relatively rare. However, Sp2 has a high potential for causing IPD including meningitis. Large-scale outbreaks of Sp2 IPD are rare and were not reported post-PCV implementation. We describe Sp2 IPD outbreak in Israel, in the PCV13 era, caused by a novel clone. Additionally, we analyzed the population structure and evolutionary dynamics of Sp2 during 2006–2018. Methods An ongoing, population-based, nationwide active surveillance, conducted since July 2009. PCV7/PCV13 were implemented in Israel in July 2009 and November 2010, respectively. All isolates were tested for antimicrobial susceptibility, PFGE, MLST and whole-genome sequencing (WGS). Results. Overall, 173 Sp2 IPD cases were identified; all isolates were analyzed by MLST (Figure 1). During 2016–2017, Sp2 caused 7.6% of all-IPD, a 7-fold increase compared with 2006–2015, and ranked second (after serotype 12F causing 12%) among IPD isolates. During 2006–2015, 98% (40/41) Sp2 IPD were caused by the previously reported global ST-1504 clone. The outbreak was caused by a novel clone ST-13578, not previously reported (Figure 2). WGS analysis confirmed that ST-13578 was related, but genetically distinct from ST-1504, observed exclusively before the outbreak. A single strain of clone ST-74 previously globally reported was identified in 2017–2018. An additional case was identified in an adult in the UK, following a family visit from Israel. The ST-13578 clone was identified only in the Jewish population and was mainly distributed in 3 of the 7 Israeli districts. All tested strains were penicillin-susceptible (MIC < 0.06 μg/mL). Conclusion To the best of our knowledge, this is the first widespread Sp2 outbreak since PCV13 introduction worldwide, caused by a novel clone ST-13578. The outbreak is still ongoing, although a declining trend was noted since 2017. Disclosures All Authors: No reported Disclosures.


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