scholarly journals Rapid evolution of enhanced Zika virus virulence during direct vertebrate transmission chains

2020 ◽  
Author(s):  
Kasen K. Riemersma ◽  
Anna S. Jaeger ◽  
Chelsea M. Crooks ◽  
Katarina M. Braun ◽  
James Weger-Lucarelli ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Substitution ◽  
Zika Virus ◽  
Rapid Evolution ◽  
Purifying Selection ◽  
Mammalian Host ◽  
Direct Transmission ◽  
Genetic Analyses ◽  
Vertebrate Hosts ◽  
The Impact

AbstractZika virus (ZIKV) has the unusual capacity to circumvent natural alternating mosquito-human transmission and be directly transmitted human-to-human via sexual and vertical routes. The impact of direct transmission on ZIKV evolution and adaptation to vertebrate hosts is unknown. Here we show that molecularly barcoded ZIKV rapidly adapted to a mammalian host during direct transmission chains in mice, coincident with the emergence of an amino acid substitution previously shown to enhance virulence. In contrast, little to no adaptation of ZIKV to mice was observed following chains of direct transmission in mosquitoes or alternating host transmission. Detailed genetic analyses revealed that ZIKV evolution in mice was generally more convergent and subjected to more relaxed purifying selection than in mosquitoes or alternate passages. These findings suggest that prevention of direct human transmission chains may be paramount to resist gains in ZIKV virulence.

scholarly journals Rapid evolution of enhanced Zika virus virulence during direct vertebrate transmission chains

2021 ◽  
Author(s):  
Kasen K. Riemersma ◽  
Anna S. Jaeger ◽  
Chelsea M. Crooks ◽  
Katarina M. Braun ◽  
James Weger-Lucarelli ◽  
...  
Keyword(s):  
Public Health ◽  
Zika Virus ◽  
Experimental Evolution ◽  
Rapid Evolution ◽  
Purifying Selection ◽  
Mammalian Host ◽  
Direct Transmission ◽  
Rapid Adaptation ◽  
Vertebrate Hosts ◽  
The Impact

Zika virus (ZIKV) has the unusual capacity to circumvent natural alternating mosquito-human transmission and be directly transmitted human-to-human via sexual and vertical routes. The impact of direct transmission on ZIKV evolution and adaptation to vertebrate hosts is unknown. Here we show that molecularly barcoded ZIKV rapidly adapted to a mammalian host during direct transmission chains in mice, coincident with the emergence of an amino acid substitution previously shown to enhance virulence. In contrast, little to no adaptation of ZIKV to mice was observed following chains of direct transmission in mosquitoes or alternating host transmission. Detailed genetic analyses revealed that ZIKV evolution in mice was generally more convergent and subjected to more relaxed purifying selection than in mosquitoes or alternate passages. These findings suggest that prevention of direct human transmission chains may be paramount to resist gains in ZIKV virulence. Importance We used experimental evolution to model chains of direct and indirect Zika virus (ZIKV) transmission by serially passaging a synthetic swarm of molecularly barcoded ZIKV within and between mosquitoes and mice. We observed that direct mouse transmission chains facilitated a rapid increase in ZIKV replication and enhanced virulence in mice. These findings demonstrate that ZIKV is capable of rapid adaptation to a vertebrate host and indicate that direct human-to-human transmission could pose a greater threat to public health than currently realized.

scholarly journals Molecular Analysis of SARS-CoV-2 Genetic Lineages in Jordan: Tracking the Introduction and Spread of COVID-19 UK Variant of Concern at a Country Level

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 302
Author(s):  
Malik Sallam ◽  
Azmi Mahafzah
Keyword(s):  
Amino Acid ◽  
Amino Acid Substitution ◽  
Rapid Evolution ◽  
Molecular Signature ◽  
Special Focus ◽  
Genetic Lineage ◽  
Synonymous Mutation ◽  
Spike Gene ◽  
Genetic Lineages ◽  
The Uk

The rapid evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is manifested by the emergence of an ever-growing pool of genetic lineages. The aim of this study was to analyze the genetic variability of SARS-CoV-2 in Jordan, with a special focus on the UK variant of concern. A total of 579 SARS-CoV-2 sequences collected in Jordan were subjected to maximum likelihood and Bayesian phylogenetic analysis. Genetic lineage assignment was undertaken using the Pango system. Amino acid substitutions were investigated using the Protein Variation Effect Analyzer (PROVEAN) tool. A total of 19 different SARS-CoV-2 genetic lineages were detected, with the most frequent being the first Jordan lineage (B.1.1.312), first detected in August 2020 (n = 424, 73.2%). This was followed by the second Jordan lineage (B.1.36.10), first detected in September 2020 (n = 62, 10.7%), and the UK variant of concern (B.1.1.7; n = 36, 6.2%). In the spike gene region, the molecular signature for B.1.1.312 was the non-synonymous mutation A24432T resulting in a deleterious amino acid substitution (Q957L), while the molecular signature for B.1.36.10 was the synonymous mutation C22444T. Bayesian analysis revealed that the UK variant of concern (B.1.1.7) was introduced into Jordan in late November 2020 (mean estimate); four weeks earlier than its official reporting in the country. In Jordan, an exponential increase in COVID-19 cases due to B.1.1.7 lineage coincided with the new year 2021. The highest proportion of phylogenetic clustering was detected for the B.1.1.7 lineage. The amino acid substitution D614G in the spike glycoprotein was exclusively present in the country from July 2020 onwards. Two Jordanian lineages dominated infections in the country, with continuous introduction/emergence of new lineages. In Jordan, the rapid spread of the UK variant of concern should be monitored closely. The spread of SARS-CoV-2 mutants appeared to be related to the founder effect; nevertheless, the biological impact of certain mutations should be further investigated.

scholarly journals The amino acid substitution affects cellular response to mistranslation

2021 ◽  
Author(s):  
Matthew D. Berg ◽  
Yanrui Zhu ◽  
Bianca Y. Ruiz ◽  
Raphaël Loll-Krippleber ◽  
Joshua Isaacson ◽  
...  
Keyword(s):  
Amino Acid ◽  
Heat Shock ◽  
Amino Acid Substitution ◽  
Heat Shock Response ◽  
Cellular Response ◽  
Genetic Interactions ◽  
Similar Frequency ◽  
Proteotoxic Stress ◽  
Shock Response ◽  
The Impact

Mistranslation, the mis-incorporation of an amino acid not specified by the standard genetic code, occurs in all organisms. tRNA variants that increase mistranslation arise spontaneously and engineered tRNAs can achieve mistranslation frequencies approaching 10% in yeast and bacteria. Interestingly, human genomes contain tRNA variants with the potential to mistranslate. Cells cope with increased mistranslation through multiple mechanisms, though high levels cause proteotoxic stress. The goal of this study was to compare the genetic interactions and the impact on transcriptome and cellular growth of two tRNA variants that mistranslate at a similar frequency but create different amino acid substitutions in Saccharomyces cerevisiae. One tRNA variant inserts alanine at proline codons whereas the other inserts serine for arginine. Both tRNAs decreased growth rate, with the effect being greater for arginine to serine than for proline to alanine. The tRNA that substituted serine for arginine resulted in a heat shock response. In contrast, heat shock response was minimal for proline to alanine substitution. Further demonstrating the significance of the amino acid substitution, transcriptome analysis identified unique up- and downregulated genes in response to each mistranslating tRNA. Number and extent of negative synthetic genetic interactions also differed depending upon type of mistranslation. Based on the unique responses observed for these mistranslating tRNAs, we predict that the potential of mistranslation to exacerbate diseases caused by proteotoxic stress depends on the tRNA variant. Furthermore, based on their unique transcriptomes and genetic interactions, different naturally occurring mistranslating tRNAs have the potential to negatively influence specific diseases.

scholarly journals Fluoroquinolone Resistance in Clinical Isolates ofStreptococcus pneumoniae: Contributions of Type II Topoisomerase Mutations and Efflux to Levels of Resistance

2000 ◽  
Vol 44 (11) ◽  
pp. 3049-3054 ◽  
Author(s):  
Darrin J. Bast ◽  
Donald E. Low ◽  
Carla L. Duncan ◽  
Laurie Kilburn ◽  
Lionel A. Mandell ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Substitution ◽  
Clinical Isolates ◽  
Fluoroquinolone Resistance ◽  
Amino Acid Substitutions ◽  
Type Ii ◽  
Low Level ◽  
High Level ◽  
The Impact ◽  
Level Resistance

ABSTRACT We report on amino acid substitutions in the quinolone resistance-determining region of type II topisomerases and the prevalence of reserpine-inhibited efflux for 70 clinical isolates ofS. pneumoniae for which the ciprofloxacin MIC is ≥4 μg/ml and 28 isolates for which the ciprofloxacin MIC is ≤2 μg/ml. The amino acid substitutions in ParC conferring low-level resistance (MICs, 4 to 8 μg/ml) included Phe, Tyr, and Ala for Ser-79; Asn, Ala, Gly, Tyr, and Val for Asp-83; Asn for Asp-78; and Pro for Ala-115. Isolates with intermediate-level (MICs, 16 to 32 μg/ml) and high-level (MICs, 64 μg/ml) resistance harbored substitutions of Phe and Tyr for Ser-79 or Asn and Ala for Asp-83 in ParC and an additional substitution in GyrA which included either Glu-85-Lys (Gly) or Ser-81-Phe (Tyr). Glu-85-Lys was found exclusively in isolates with high-level resistance. Efflux contributed primarily to low-level resistance in isolates with or without an amino acid substitution in ParC. The impact of amino acid substitutions in ParE was minimal, and no substitutions in GyrB were identified.

scholarly journals Impact of extrinsic incubation temperature on natural selection during Zika virus infection of Aedes aegypti

2021 ◽  
Author(s):  
Reyes A. Murrieta ◽  
Selene Garcia-Luna ◽  
Deedra J. Murrieta ◽  
Gareth Halladay ◽  
Michael C. Young ◽  
...  
Keyword(s):  
Aedes Aegypti ◽  
Positive Selection ◽  
Aedes Albopictus ◽  
Zika Virus ◽  
Vector Competence ◽  
Purifying Selection ◽  
The Impact ◽  
Selective Environment ◽  
Mosquito Infection ◽  
Fluctuating Temperatures

AbstractArthropod-borne viruses (arboviruses) require replication across a wide range of temperatures to perpetuate. While vertebrate hosts tend to maintain temperatures of approximately 37°C - 40°C, arthropods are subject to ambient temperatures which can have a daily fluctuation of > 10°C. Temperatures impact vector competence, extrinsic incubation period, and mosquito survival unimodally, with optimum occurring at some intermediate temperature. In addition, the mean and range of daily temperature fluctuations influence arbovirus perpetuation and vector competence. The impact of temperature on arbovirus genetic diversity during systemic mosquito infection, however, is poorly understood. Therefore, we determined how constant extrinsic incubation temperatures of 25°C, 28°C, 32°C, and 35°C control Zika virus (ZIKV) vector competence and population dynamics within Aedes aegypti and Aedes albopictus mosquitoes. We also examined diurnally fluctuating temperatures which more faithfully mimic field conditions in the tropics. We found that vector competence varied in a unimodal manner for constant temperatures peaking between 28°C and 32°C for both Aedes species. Transmission peaked at 10 days post-infection for Aedes aegypti and 14 days for Aedes albopictus. The effect of diurnal temperature was distinct and could not have been predicted from constant temperature-derived data. Using RNA-seq to characterize ZIKV population structure, we identified that temperature alters the selective environment in unexpected ways. During mosquito infection, constant temperatures more often elicited positive selection whereas diurnal temperatures led to strong purifying selection in both Aedes species. These findings demonstrate that temperature has multiple impacts on ZIKV biology within mosquitoes, including major effects on the selective environment within mosquitoes.Author SummaryArthropod-borne viruses (arboviruses) have emerged in recent decades due to complex factors that include increases in international travel and trade, the breakdown of public health infrastructure, land use changes, and many other factors. Climate change also has the potential to shift the geographical ranges of arthropod vectors, consequently increasing the global risk of arbovirus infection. Changing temperatures may also alter the virus-host interaction, ultimately resulting in the emergence of new viruses and virus genotypes in new areas. Therefore, we sought to characterize how temperature (both constant and fluctuating) alters the ability of Aedes aegypti and Aedes albopictus to transmit Zika virus, and how it influences virus populations within mosquitoes. We found that intermediate temperatures maximize virus transmission compared to more extreme and fluctuating temperatures. Constant temperatures increased positive selection on virus genomes, while fluctuating temperatures strengthened purifying selection. Our studies provide evidence that in addition to altering VC, temperature significantly influences the selective environment within mosquitoes.

scholarly journals The amino acid substitution affects cellular response to mistranslation

2021 ◽  
Author(s):  
Matthew D Berg ◽  
Yanrui Zhu ◽  
Bianca Y Ruiz ◽  
Raphaël Loll-Krippleber ◽  
Joshua Isaacson ◽  
...  
Keyword(s):  
Amino Acid ◽  
Heat Shock ◽  
Amino Acid Substitution ◽  
Heat Shock Response ◽  
Cellular Response ◽  
Genetic Interactions ◽  
Similar Frequency ◽  
Proteotoxic Stress ◽  
Shock Response ◽  
The Impact

Abstract Mistranslation, the mis-incorporation of an amino acid not specified by the “standard” genetic code, occurs in all organisms. tRNA variants that increase mistranslation arise spontaneously and engineered tRNAs can achieve mistranslation frequencies approaching 10% in yeast and bacteria. Interestingly, human genomes contain tRNA variants with the potential to mistranslate. Cells cope with increased mistranslation through multiple mechanisms, though high levels cause proteotoxic stress. The goal of this study was to compare the genetic interactions and the impact on transcriptome and cellular growth of two tRNA variants that mistranslate at a similar frequency but create different amino acid substitutions in Saccharomyces cerevisiae. One tRNA variant inserts alanine at proline codons whereas the other inserts serine for arginine. Both tRNAs decreased growth rate, with the effect being greater for arginine to serine than for proline to alanine. The tRNA that substituted serine for arginine resulted in a heat shock response. In contrast, heat shock response was minimal for proline to alanine substitution. Further demonstrating the significance of the amino acid substitution, transcriptome analysis identified unique up- and downregulated genes in response to each mistranslating tRNA. Number and extent of negative synthetic genetic interactions also differed depending upon type of mistranslation. Based on the unique responses observed for these mistranslating tRNAs, we predict that the potential of mistranslation to exacerbate diseases caused by proteotoxic stress depends on the tRNA variant. Furthermore, based on their unique transcriptomes and genetic interactions, different naturally occurring mistranslating tRNAs have the potential to negatively influence specific diseases.

Hubsm: A Novel Amino Acid Substitution Matrix for Comparing Hub Proteins

2017 ◽  
Vol 7 (8) ◽  
pp. 212
Author(s):  
Renganayaki G. ◽  
Achuthsankar S. Nair
Keyword(s):  
Amino Acid ◽  
Amino Acid Substitution ◽  
Low Complexity ◽  
Database Search ◽  
Substitution Matrix ◽  
Compositional Bias ◽  
Sequence Alignments ◽  
Amino Acid Substitution Matrix ◽  
Alignment Algorithms ◽  
Hub Proteins

Sequence alignment algorithms and  database search methods use BLOSUM and PAM substitution matrices constructed from general proteins. These de facto matrices are not optimal to align sequences accurately, for the proteins with markedly different compositional bias in the amino acid.   In this work, a new amino acid substitution matrix is calculated for the disorder and low complexity rich region of Hub proteins, based on residue characteristics. Insights into the amino acid background frequencies and the substitution scores obtained from the Hubsm unveils the  residue substitution patterns which differs from commonly used scoring matrices .When comparing the Hub protein sequences for detecting homologs,  the use of this Hubsm matrix yields better results than PAM and BLOSUM matrices. Usage of Hubsm matrix can be optimal in database search and for the construction of more accurate sequence alignments of Hub proteins.

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