China
Africa
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Out of Nowhere
Published in Rae-Ellen W. Kavey, Allison B. Kavey, Viral Pandemics, 2020
Rae-Ellen W. Kavey, Allison B. Kavey
Analysis of these four pandemics does not support the “out of nowhere” concept, but instead highlights important themes in contemporary viral pandemic development: the critical roles of ongoing viral evolution and of emerging viruses that can cross over from other species to infect humans; the very high importance of global travel in disease introduction to new populations; the speed of disease spread in our crowded, increasingly connected world; and the importance of global scientific communication and collaboration. Critical evaluation of an outbreak focused on these characteristics could potentially interrupt disease spread.
Introduction to virus structure, classification, replication, and hosts
Published in Avindra Nath, Joseph R. Berger, Clinical Neurovirology, 2020
Philippe Simon, Kevin M. Coombs
A clinically and virologically relevant phenomenon common to all living organisms is the insertion of mutations during genomic replication. In the case of bacteria, this can rapidly lead to the emergence of antibiotic resistance and mutants with altered virulence and metabolic activities. The same phenomenon is present in viral replication, with RNA polymerases being notoriously error prone. DNA viruses have been estimated to mutate in the range of 10−8 to 10−6 substitutions per nucleotide per cell infection (s/n/c) whereas RNA virus mutates in the 10−6 to 10−4 range [25]. In simpler terms, for an RNA virus with a genome in the 104 nt range (e.g., influenza virus) one would expect, on average, every progeny virus within each cell to contain a genomic mutation. In the case of influenza viruses and HIV, this can rapidly lead to resistance to antiviral drugs, severely limiting therapeutic options. Another result of this property is that viral evolution can occur within an infected individual whereby the viral output following infection with a clonal population will contain a multitude of quasi-species.
Evolution
Published in Paul Pumpens, Single-Stranded RNA Phages, 2020
Thus, according to Bollback and Huelsenbeck (2001), the ancestral phage genome increased in size on the order of 600 nucleotides after the divergence of the Allolevivirus and Levivirus lineages, but before the diversification of the Allolevivirus lineage, by either recombination or intramolecular duplication. A number of additional changes appeared to have been coupled with this genome expansion: notably, the loss of the lysis coding region, the evolution of a novel readthrough protein, and an increase in translation of the maturation protein. An increase in the genome size might be implicated in catalyzing all of these changes via changing the secondary structure of the RNA molecule. The lack of the lysis gene in the Allolevivirus was compensated for by the higher levels of the maturation protein which functioned in the phage release. Although the genome evolution in viruses was typically believed to be characterized by an economization of the genome, Bollback and Huelsenbeck (2001) indicated that increases in genome size might have played an important role in viral evolution.
Should we be vaccinating children against COVID-19 in high-income countries?
Published in Expert Review of Vaccines, 2021
Grace Li, Adam Finn, Andrew J. Pollard
For maximum and fastest impact, national programs need to prioritize high two-dose coverage in adults, especially the elderly and those with co-morbidities over administration of vaccines to younger age cohorts. More broadly, global health leaders [22,23] have emphasized the need to prioritize vulnerable adults in low- and middle-income countries over children in high-income countries. COVID-19 vaccination rollout has again highlighted global inequality in access to medicines; as of June 5, only 1.6% of global vaccine doses have been administered in Africa (35 million of a total of 2 billion doses given so far), with Europe and the US accounting for 36% of doses administered to date whilst representing 17% of the global population. There is a moral argument that vulnerable adults in low- and middle-income countries who are at greater risk of dying from COVID-19 disease should be prioritized for vaccination over children at low-risk in high-income countries, while global supply of vaccine is constrained. Aside from considerations of equity, failure to minimize viral replication and large epidemic waves around the world will hasten viral evolution and the spread of variants that are either more transmissible, better able to evade naturally acquired and/or vaccine-induced immunity or both – as has recently occurred with the delta variant now rapidly proliferating in many countries. Unless available vaccine doses are used strategically to maximum effect around the world, everyone will suffer, not just the inhabitants of poorer countries.
Ravaging SARS-CoV-2: rudimentary diagnosis and puzzling immunological responses
Published in Current Medical Research and Opinion, 2021
Tapan Kumar Mukherjee, Parth Malik, Radhashree Maitra, John R. Hoidal
It is further noted that RNA viruses are notorious for high mutation rates which can occur a million times faster than that of their hosts. This feature is a primary reason why we need an influenza vaccine every year. The mutagenic capability of a virus depends upon several factors, including the fidelity of viral enzymes that replicate nucleic acids. In the case of SARS-CoV-2, the fidelity of the RNA dependent RNA polymerase (RdRp) is critical. Mutation rates drive viral evolution and genome variability, thereby enabling the virus to escape host immunity and develop drug resistance20. Pachetti et al. reported that the viral genomes present different point mutations, distinguishable within different geographic areas. Three recurrent mutations were identified in Europe (in positions 3036, 14,408 and 23,403) and three different mutations were identified in North America (in positions 17,746, 17,857 and 18,060). These mutations are yet to be detected in Asia. However, the number and occurrence, as well as the median value of virus point mutations identified in Asia, is ever increasing.
Zika virus pathogenesis and current therapeutic advances
Published in Pathogens and Global Health, 2021
Caroline Mwaliko, Raphael Nyaruaba, Lu Zhao, Evans Atoni, Samuel Karungu, Matilu Mwau, Dimitri Lavillette, Han Xia, Zhiming Yuan
The second function of sfRNAs is suppression of IFN responses in vertebrates. ZIKV sfRNA functions both as a RIG-1 and MDA-5 agonist and has stronger activity than DENV serotype 2, which only affects RIG-1 [68]. In WNV, sfRNAs directly antagonize IFN- stimulated gene (ISG) products, such as protein kinase R and RNase L, which bind RNAs [69]. DENV sfRNA antagonizes proteins that modulate viral infection, which include G3BP1, G3BP2, and CAPRIN1, colocalizing with them. Most flaviviruses produce and use this type of RNA in their mechanisms of interacting with the host. sfRNA was first characterized in Murray Valley Viral infections [72] and was later found in Japanese Encephalitis Virus (JEV) [73] and WNV [74]. sfRNAs help flaviviruses evade the innate immune system [69,75,76]. Mutations in sfRNA, such as deletions, lead to significant effects on the viral replication and life cycle of DENV and WNV in cells that exhibit IFN I responses [69,77]. These mutations may also be the cause of the emergence of new pathogenic viral strains as a result of viral evolution [78].