Mutations and Variants of SARS-CoV-2, the Coronavirus Causing COVID-19

2021 ◽  
Vol 30 (6) ◽  
pp. 566-585
Author(s):  
Luchezar Karagyozov ◽  

In 2020, the SARS-CoV-2 coronavirus caused a pandemic with severe consequences for many countries. The life cycle of the virus is briefly described. It is noted that the multiplication of viral genetic material is accompanied by the emergence of mutations, which leads to the emergence of new viral variants. Viral variants may differ in their effectiveness in infecting, spreading, in the severity of the disease they cause, and in their ability to escape acquired immunity. The most important SARS-CoV-2 variants that have emerged so far are discussed. The need for global monitoring of the emergence of new variants and rapid and mass vaccination to tackle the pandemic is emphasized.

2021 ◽  
Author(s):  
Toril Lindback ◽  
Annette Fagerlund ◽  
Marina Elisabeth Aspholm ◽  
Grzegorz Wegrzyn

Shiga toxin (Stx) is the major virulence factor of enterohemorrhagic Escherichia coli (EHEC), and the stx genes are carried by temperate bacteriophages (Stx phages). The switch between lysogenic and lytic life cycle of the phage, which is crucial for Stx production and for severity of the disease, is regulated by the CI repressor. CI maintain latency by preventing transcription of the replication proteins. Three EHEC phage replication units (Eru1-3) in addition to the classical lambdoid replication region have been described previously, and Stx phages carrying the Eru1 replication region were associated with highly virulent EHEC strains. In this study, we have classified the Eru replication region of 419 Stx phages. In addition to the lambdoid replication region and the three already described Erus, ten novel Erus (named Eru4 to Eru13) were detected. The lambdoid type, Eru1, Eru4 and Eru7 seem to be widely distributed in Western Europe. Notably, EHEC strains involved in severe outbreaks in England and Norway carry Stx phages with Eru1, Eru2, Eru5 and Eru7 replication regions. Phylogenetic analysis of CI repressors from Stx phages revealed eight major clades that largely separate according to Eru type. The classification of replication regions and CI proteins of Stx phages provides an important platform for further studies aimed to assess how characteristics of the replication region influence the regulation of phage life cycle and, consequently, the virulence potential of the host EHEC strain. IMPORTANCE: EHEC is an emerging health challenge worldwide and outbreaks caused by this pathogen tend to be more frequent and severe. Increased knowledge on how characteristics of the replication region influence the virulence of E. coli may be used for more precise identification of high-risk EHEC strains.


Author(s):  
Jan A. Pechenik

I have a Hardin cartoon on my office door. It shows a series of animals thinking about the meaning of life. In sequence, we see a lobe-finned fish, a salamander, a lizard, and a monkey, all thinking, “Eat, survive, reproduce; eat, survive, reproduce.” Then comes man: “What's it all about?” he wonders. Organisms live to reproduce. The ultimate selective pressure on any organism is to survive long enough and well enough to pass genetic material to a next generation that will also be successful in reproducing. In this sense, then, every morphological, physiological, biochemical, or behavioral adaptation contributes to reproductive success, making the field of life cycle evolution a very broad one indeed. Key components include mode of sexuality, age and size at first reproduction (Roff, this volume), number of reproductive episodes in a lifetime, offspring size (Messina and Fox, this volume), fecundity, the extent to which parents protect their offspring and how that protection is achieved, source of nutrition during development, survival to maturity, the consequences of shifts in any of these components, and the underlying mechanisms responsible for such shifts. Many of these issues are dealt with in other chapters. Here I focus exclusively on animals, and on a particularly widespread sort of life cycle that includes at least two ecologically distinct free-living stages. Such “complex life cycles” (Istock 1967) are especially common among amphibians and fishes (Hall and Wake 1999), and within most invertebrate groups, including insects (Gilbert and Frieden 1981), crustaceans, bivalves, gastropods, polychaete worms, echinoderms, bryozoans, and corals and other cnidarians (Thorson 1950). In such life cycles, the juvenile or adult stage is reached by metamorphosing from a preceding, free-living larval stage. In many species, metamorphosis involves a veritable revolution in morphology, ecology, behavior, and physiology, sometimes taking place in as little as a few minutes or a few hours. In addition to the issues already mentioned, key components of such complex life cycles include the timing of metamorphosis (i.e., when it occurs), the size at which larvae metamorphose, and the consequences of metamorphosing at particular times or at particular sizes. The potential advantages of including larval stages in the life history have been much discussed.


2020 ◽  
Vol 19 (2) ◽  
pp. 5
Author(s):  
Jorge Bomfim Fróes De Farias ◽  
Antonio Pedro Fróes De Farias ◽  
Anelize Gimenez De Souza

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) called “coronavirus 2019” (COVID-19), has become a threat to the general population and health professionals worldwide [1]. The clinical features of COVID-19 is like that of other respiratory viruses, with specifically, fever, generally dry cough, tiredness and, in more severe cases, dyspnea, pulmonary bleeding, severe lymphopenia and renal failure [2].For diagnosis, the World Health Organization (WHO) recommends the collection of samples from the upper or lower respiratory tract. In the laboratory, the amplification of the genetic material extracted from the saliva or mucus sample is carried out by means of a reverse transcription followed by a polymerase chain reaction (RT-PCR), which involves the synthesis of a double-stranded DNA molecule from of an RNA template, in the search for conserved parts of the coronavirus genetic code. In patients with a confirmed diagnosis, the laboratory test should be repeated to assess the release of viral particles, before leaving the isolation [3]. The clinical manifestation and severity of the disease is directly related to the health condition of the infected individual. Symptoms are often mild as in a common cold or flu and it can progress to pneumonia. Ventilatory support therapy such as oxygen therapy and/or mechanical ventilation is necessary as an intervention method in the most severe cases of the disease [4]. Individuals with chronic respiratory diseases and other comorbidities can present the most severe form of COVID-19 and, for this reason, care with prevention should be emphasized [5]...


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 468-468
Author(s):  
Marie Lia ◽  
Amanda Carette ◽  
Hongyan Tang ◽  
Qiong Shen ◽  
Tongwei Mo ◽  
...  

Abstract Abstract 468 Deletion of chromosomal region 13q14 represents the most common genetic aberration in chronic lymphocytic leukemia (CLL) and occurs with less frequency in other lymphoid malignancies. 13q14 deletions are commonly large and heterogeneous in size, affecting multiple genes. We recently demonstrated that the targeted deletion in mice of miR-15a/16-1 alone causes lymphoproliferations and recapitulates the spectrum of CLL-associated phenotypes in humans. However, both the penetrance and severity of the disease increased markedly upon deletion of the 110 kilobase (kb)-long minimal deleted region (MDR) that encompasses the DLEU2/miR-15a/16-1 cluster (Klein et al., Cancer Cell, 2010). Thus, we investigate here the extent to which the additional deletion of genetic material encoded in the 690 kb large genomic region telomeric of the MDR, including the DLEU7 and RNASEH2B genes, affects the phenotype and spectrum of lymphoproliferations and disease course. To this end, we generated a conditional allele that allows in vivo deletion of this 800 kb large region termed common deleted region (CDR) specifically in B cells. B-cell conditional deletion was necessary since homozygous CDR germ-line deletion led to embryonic lethality. We demonstrate the technical feasibility of mimicking a large chromosomal deletion (800 kb) occurring in human cancer in vivo and in a cell type-specific fashion, thus establishing an animal model for this genomic aberration. We found that despite a similar time-point of disease onset (∼12 months) and disease penetrance (∼40%), the spectrum of lymphoproliferations developing in CDR-deleted mice differed from those found in MDR-deleted mice in that the fraction of CLL among the various types of B-lymphoproliferations (including CLL, CD5+ monoclonal B-cell lymphocytosis (MBL) and CD5– non-Hodgkin lymphomas (NHL)) was significantly elevated. Specifically, 19/20 mice with homozygous deletion of the CDR developed lymphoproliferations that represented CLL (95% CLL; 5% MBL) vs. 12/22 of the corresponding MDR-deleted mice (55% CLL; 27% MBL; 18% NHL). Since we previously observed that MDR+/– mice compared to wild-type mice showed a trend towards developing clonal lymphoproliferations, we established and monitored cohorts of CDR+/– mice and wild-type littermates. 25% of CDR+/– mice developed CD5+ lymphoproliferations vs. 8% of control mice. Determination of event-free survival demonstrated that CDR+/– mice succumb to their disease earlier than wild-type littermates (P=0.0002). Compared to MDR+/– mice, the CDR+/– mice showed a trend towards a more aggressive disease course (70% of CDR+/– vs. 45% of MDR+/– mice have died at 20 months). In summary, these results suggest that the additional loss of genetic elements located telomeric of the MDR impacts the phenotype of the lymphoproliferations and potentially the severity of disease. Notably, lymphoproliferations derived from 4 independent CLL mouse models, i.e. TCL1-tg (Yan et al., PNAS, 2006) as well as miR-15a/16-1, MDR (Klein et al., Cancer Cell, 2010) and CDR-deleted mice, expressed antibody genes with nearly identical, stereotypic antigen binding regions. Specifically, comparing all HCDR3 regions derived from MBL or CLL cases of our own (n=46) and the TCL1-tg (n=20) studies, we observed that 44% (29/66) of the junctions can be assigned to 8 sets of highly similar HCDR3 regions among the sequence collection, 5 of which have previously been defined by Yan et al. These findings provide a rationale for defining clusters of stereotypic antigen receptors in CLL-prone mice. They also suggest that genetic aberrations disrupting the control of cell growth and survival and chronic antigen-stimulation co-operate in the clonal expansion of CLL tumor cells. In summary, published and the present results suggest that whereas deletion of the miR-15a/16-1 cluster is the critical mechanism in the pathogenesis of CLL with 13q14 aberrations, the additional loss of genetic elements encoded in the 13q14 tumor suppressor locus can significantly influence the penetrance of the phenotype, the spectrum of the lymphoproliferations, and the severity of the disease course. Since 13q14 deletions in humans are usually heterogeneous, these findings provide a clear rationale for determining the pathogenic role of the various genetic elements affected by deletions of the 13q14 locus. Disclosures: No relevant conflicts of interest to declare.


1974 ◽  
Vol 16 (2) ◽  
pp. 285-296 ◽  
Author(s):  
Gilbert L. Schroeter ◽  
Godfrey M. Hewitt

The chiasma frequencies in males of three species of grasshopper with and without B-chromosomes and supernumerary segments were scored at diplotene. The partially heterochromatic B's found in some individuals of Chimarocephala pacifica pacifica have no effect on chiasma frequencies. On the other hand, heterochromatic supernumerary segments in Oedaleonotus phryneicus males significantly increase the mean chiasma frequencies over individuals without them but not the between-cell variances. In Camnula pellucida neither the mitotically unstable B's nor supernumerary segments have any apparent effect on chiasma.frequencies. The supernumerary elements in Chimarocephala pacifica and Camnula pellucida may, however, produce other effects during the life cycle These and previous observations suggest that polymorphism involving extra genetic material in grasshoppers can result in increased population variability via two different means: (1) by producing variation in chiasma frequency or (2) through direct effects in the individuals possessing it. The importance of such a mechanism for producing variation is discussed.


Author(s):  
Wollela Behja ◽  
Mudin Jemal

Viruses are the smallest infectious agents of animal and plant tissues. Viruses are totally dependent on living cells to survive as they utilize the host cell's own replication processes, in order to reproduce themselves. HIV is the causative agent of AIDS. HIV is an unusually difficult to treat because it incorporate its own genetic material into the genome of an infected host cell. It infects T cells that carry the CD4 antigen on their surface. Binding and fusion, reverse transcription, integration, transcription, assembly and budding are the major steps of the HIV life cycle. The HIV/AIDS disease is treated by interrupting the HIV life cycle with specially designed drugs. The discovery of effective drugs against HIV has focused on targeting various critical components of the replication cycle of HIV. Depending on the target within the HIV replicative cycle they interact with, anti-HIV compounds are categorized into six groups. These are: nucleoside (nucleotide) reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), cell entry inhibitors or fusion inhibitors (FIs), co-receptor inhibitors (CRIs) and integrase inhibitors (INIs). The development of effective anti-HIV drugs is difficult due to wide variations in nucleotide and amino acid sequences. The development of anti-HIV drug passes through several important steps. This includes development from α-APA to ITU, ITU to DATA, DAPY to etravirine. Fosdevirine, lersivirine and rilpivirine are among the drugs that were undergoing clinical development and finally only rilpivirine was approved by FDA. The synthesis of delavirdine employs the use of heterocyclic rings like substituted pyridine and indole.


1999 ◽  
Vol 67 (12) ◽  
pp. 6369-6374 ◽  
Author(s):  
Karen P. Piper ◽  
Rhian E. Hayward ◽  
Martin J. Cox ◽  
Karen P. Day

ABSTRACT Why there are so few gametocytes (the transmission stage of malaria) in the blood of humans infected with Plasmodiumspp. is intriguing. This may be due either to reproductive restraint by the parasite or to unidentified gametocyte-specific immune-mediated clearance mechanisms. We propose another mechanism, a cross-stage immunity to Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP-1). This molecule is expressed on the surface of the erythrocyte infected with either trophozoite or early gametocyte parasites. Immunoglobulin G antibodies to PfEMP-1, expressed on both life cycle stages, were measured in residents from an area where malaria is endemic, Papua New Guinea. Anti-PfEMP-1 prevalence increased with age, mirroring the decline in both the prevalence and the density of asexual and transmission stages in erythrocytes. These data led us to propose that immunity to PfEMP-1 may influence malaria transmission by regulation of the production of gametocytes. This regulation may be achieved in two ways: (i) by controlling asexual proliferation and density and (ii) by affecting gametocyte maturation.


2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Victor Raul Camargo Ortega ◽  
Leliette Deyanira Bravo López ◽  
Angel Visoso Salgado ◽  
Fernando Mejia Sanchez ◽  
Julieta Castillo Cadena

Background. Although the direct cause of chronic periodontitis is bacterial infection, the progression of this disease depends on genetic and environmental factors, and smoking is a known risk factor in the development and severity of the disease. An individual’s susceptibility may be influenced by polymorphisms in the glutathione S-transferase genes. These genes encode enzymes that metabolize xenobiotic compounds. The aim of this study was to determine the frequency of GSTM1, GSTT1, and GSTP1 polymorphisms in Mexicans with chronic periodontitis. Methods. 60 Mexicans with chronic periodontitis (30 smokers and 30 nonsmokers) were studied. A peripheral blood sample was taken for subsequent DNA extraction. The genetic material was PCR-amplified followed by restriction fragment length polymorphism with the aim of identifying GST polymorphisms. Results. Polymorphisms in the GSTT1 and GSTP1 genes were not significantly different between the smokers and nonsmokers. However, there were significant differences (P=0.05) between groups in polymorphisms in the GSTM1 gene. The patients with chronic periodontitis have a higher frequency of null and mutant polymorphisms in GSTM1, GSTT1, and GSTP1 compared with historical data from a healthy Mexican population. Conclusions. The presence of these polymorphisms may be a risk factor for the development of chronic periodontitis.


2021 ◽  
Vol 22 (7) ◽  
pp. 3558
Author(s):  
Manuel J. Rial ◽  
José A. Cañas ◽  
José M. Rodrigo-Muñoz ◽  
Marcela Valverde-Monge ◽  
Beatriz Sastre ◽  
...  

There is currently enough evidence to think that miRNAs play a role in several key points in asthma, including diagnosis, severity of the disease, and response to treatment. Cells release different types of lipid double-membrane vesicles into the extracellular microenvironment, including exosomes, which function as very important elements in intercellular communication. They are capable of distributing genetic material, mRNA, mitochondrial DNA, and microRNAs (miRNAs). Serum miRNA screening was performed in order to analyze possible changes in serum miRNAs in 10 patients treated with reslizumab and 6 patients with mepolizumab after 8 weeks of treatment. The expression of miR-338-3p was altered after treatment (p < 0.05), although no significant differences between reslizumab and mepolizumab were found. Bioinformatic analysis showed that miR-338-3p regulates important pathways in asthma, such as the MAPK and TGF-β signaling pathways and the biosynthesis/degradation of glucans (p < 0.05). However, it did not correlate with an improvement in lung function. MiRNA-338-3p could be used as a biomarker of early response to reslizumab and mepolizumab in severe eosinophilic asthmatic patients. In fact, this miRNA could be involved in airway remodeling, targeting genes related to MAPK and TGF-β signaling pathways.


2020 ◽  
pp. jbc.RA120.016148
Author(s):  
Caroline B. Plescia ◽  
Emily A. David ◽  
Dhabaleswar Patra ◽  
Ranjan Sengupta ◽  
Souad Amiar ◽  
...  

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first discovered in December 2019 in Wuhan, China and expeditiously spread across the globe causing a global pandemic. Research on SARS-CoV-2, as well as the closely related SARS-CoV-1 and MERS coronaviruses is restricted to BSL-3 facilities. Such BSL-3 classification make SARS-CoV-2 research inaccessible to the majority of functioning research laboratories in the US; this becomes problematic when the collective scientific effort needs to be focused on such in the face of a pandemic. However, a minimal system capable of recapitulating different steps of the viral life cycle without using the virus’ genetic material could increase accessibility.  In this work, we assessed the four structural proteins from SARS-CoV-2 for their ability to form virus-like particles (VLPs) from human cells to form a competent system for BSL-2 studies of SARS-CoV-2. Herein, we provide methods and resources of producing, purifying, fluorescently and APEX2-labeling of SARS-CoV-2 VLPs for the evaluation of mechanisms of viral budding and entry as well as assessment of drug inhibitors under BSL-2 conditions. These systems should be useful to those looking to circumvent BSL-3 work with SARS-CoV-2 yet study the mechanisms by which SARS-CoV-2 enters and exits human cells.


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