Quasispecies dynamics in disease prevention and control

Domingo, Esteban

doi:10.1016/b978-0-12-816331-3.00008-8

Cited by 4 publications

(7 citation statements)

References 139 publications

(127 reference statements)

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“…A value higher than ten is acceptable, while ten or below would signify limited efficacy. 65,67 The therapeutic window of medication is the range of medication dose which can treat a disease effectively without toxic effects.…”

Section: Resultsmentioning

confidence: 99%

Photodynamic treatment of multidrug-resistant bacterial infection using indium phosphide quantum dots

et al. 2022

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Section: Resultsmentioning

confidence: 99%

Photodynamic treatment of multidrug-resistant bacterial infection using indium phosphide quantum dots

et al. 2022

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“…Notably, a higher relative fitness and increased replication level may translate into higher excreted virus doses during infection. If higher doses are transmitted on average, this will inevitably increase the viral capability to adapt to humans [30,36]. In addition, reduced cytokine induction is often considered to be an indicator of increased virulence.…”

Section: Discussionmentioning

confidence: 99%

Functional comparison of MERS-coronavirus lineages reveals increased zoonotic potential of the recombinant lineage 5

Schroeder

Mache

Kleine-Weber

et al. 2020

Preprint

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Middle East respiratory syndrome coronavirus (MERS-CoV) can cause severe pneumonia in humans. The virus is enzootic in dromedary camels across the Middle East and Africa. It is acquired through animal contact and undergoes limited onward transmission particularly in hospitals. Because of this initial potential for human-to-human transmission, we monitor the virus for phenotypic changes related to its pandemic potential. Potential phenotypic changes have been suspected since the year 2015, when a novel recombinant clade (MERS-CoV lineage 5) caused large nosocomial outbreaks in Saudi Arabia and South Korea that effectively swept other, hitherto co-circulating viral lineages. To this day, lineage 5 remains the only circulating MERS-CoV lineage on the Arabian Peninsula. In spite of available sequence data, no studies of viral phenotype have been carried out to date. Here we performed a comprehensive in-vitro and ex-vivo comparison of live virus isolates taken in Saudi Arabia immediately before and after the shift toward lineage 5. We characterized seven isolates representing the recombination-parental lineage 3, eight isolates representing parental lineage 4, as well as eight isolates representing lineage 5. Replication of lineage 5 viruses is significantly increased over isolates from parental lineages in cell culture and ex-vivo lung models. Transcriptional profiling by real-time RT-PCR shows that several key immune genes (IFNb1, CCL5, IFNL1) are significantly less induced in lung cells infected with lineage 5 MERS-CoV compared to parental strains. In IFN receptor knock out cells, as well as under chemical inhibition of IFN signalling, the differences in replication level between lineage 5 and parental lineages are reduced, suggesting that phenotypic differences may be determined by IFN antagonism. Concordantly, lineage 5 shows increased resilience against interferon (IFN) pre-treatment of Calu-3 cells and maintains a 10-fold higher replication level under low and high concentrations of IFN. Reduced immune activation combined with enhanced virus replication and IFN resilience may explain the dominance of lineage 5 on the Arabian Peninsula. This phenotypic difference is highly relevant with regard to pandemic potential, and has remained undiscovered in spite of viral sequence surveillance.

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“…61 However, in long, perfect or near-perfect RNA duplexes, an intermediate characteristic of replicating RNA viruses, it was discovered that the enzyme ADAR-1 can cause extensive sequence modification known as hypermutagenesis. 62 In persistent measles infection, this can result in up to 50% of the Us being shifted to Cs on the complementary RNA strand. 59 Note that in DNA viruses, dsRNA can also result from bidirectional transcription in overlapping regions that gives rise to complementary transcripts.…”

Section: Antiviral Factorsmentioning

confidence: 99%

“…Other enzymes involved belong to the APOBEC family, the founding member being APOBEC1, which deaminates a C at a specific site in the human apolipoprotein B mRNA to give rise to a premature stop codon and also has other regulatory activities. 62 Similar to ADAR-1,…”

Section: Antiviral Factorsmentioning

confidence: 99%

“…As a result, the mRNA can encode shorter and longer versions of the delta antigen that share a common amino‐terminus 61 . However, in long, perfect or near‐perfect RNA duplexes, an intermediate characteristic of replicating RNA viruses, it was discovered that the enzyme ADAR‐1 can cause extensive sequence modification known as hypermutagenesis 62 . In persistent measles infection, this can result in up to 50% of the Us being shifted to Cs on the complementary RNA strand 59 .…”

Section: Hidden Structures and Activities Detectedmentioning

confidence: 99%

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Viruses as archaeological tools for uncovering ancient molecular relationships

Ariza‐Mateos,

Briones,

Perales

et al. 2023

Annals of the New York Academy of Sciences

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The entry of a virus into the host cell always implies the alteration of certain intracellular molecular relationships, some of which may involve the recovery of ancient cellular activities. In this sense, viruses are archaeological tools for identifying unexpressed activities in noninfected cells. Among these, activities that hinder virus propagation may represent cellular defense mechanisms, for example, activities that mutagenize the viral genome such as ADAR‐1 or APOBEC activities. Instead, those that facilitate virus propagation can be interpreted as the result of viral adaptation to—or mimicking—cellular structures, enabling the virus to perform anthropomorphic activities, including hijacking, manipulating, and reorganizing cellular factors for their own benefit. The alternative we consider here is that some of these second set of cellular activities were already in the uninfected cell but silenced, under the negative control of the cell or lineage, and that they represent a necessary precondition for viral infection. For example, specifically loading an amino acid at the 3'‐end of the mRNA of some plant viruses by aminoacyl‐tRNA synthetases has proved essential for virus infection despite this reaction not occurring with cellular mRNAs. Other activities of this type are discussed here, together with the biological context in which they acquire a coherent meaning, that is, genetic latency and molecular conflict.

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Quasispecies dynamics in disease prevention and control

Cited by 4 publications

References 139 publications

Photodynamic treatment of multidrug-resistant bacterial infection using indium phosphide quantum dots

Photodynamic treatment of multidrug-resistant bacterial infection using indium phosphide quantum dots

Functional comparison of MERS-coronavirus lineages reveals increased zoonotic potential of the recombinant lineage 5

Viruses as archaeological tools for uncovering ancient molecular relationships

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