scholarly journals SARS-CoV-2 Sequence Characteristics of COVID-19 Persistence and Reinfection

2021 ◽  
Author(s):  
Manish C Choudhary ◽  
Charles R Crain ◽  
Xueting Qiu ◽  
William Hanage ◽  
Jonathan Z Li
Keyword(s):  
Persistent Infection ◽  
Viral Evolution ◽  
Phylogenetic Reconstruction ◽  
Geographic Region ◽  
Antibody Treatment ◽  
Viral Genomes ◽  
Monoclonal Antibody Treatment ◽  
Viral Sequences ◽  
Sequence Characteristics ◽  
Baseline Health

Abstract Background Both SARS-CoV-2 reinfection and persistent infection have been reported, but sequence characteristics in these scenarios have not been described. We assessed published cases of SARS-CoV-2 reinfection and persistence, characterizing the hallmarks of reinfecting sequences and the rate of viral evolution in persistent infection. Methods A systematic review of PubMed was conducted to identify cases of SARS-CoV-2 reinfection and persistence with available sequences. Nucleotide and amino acid changes in the reinfecting sequence were compared to both the initial and contemporaneous community variants. Time-measured phylogenetic reconstruction was performed to compare intra-host viral evolution in persistent SARS-CoV-2 to community-driven evolution. Results Twenty reinfection and nine persistent infection cases were identified. Reports of reinfection cases spanned a broad distribution of ages, baseline health status, reinfection severity, and occurred as early as 1.5 months or >8 months after the initial infection. The reinfecting viral sequences had a median of 17.5 nucleotide changes with enrichment in the ORF8 and N genes. The number of changes did not differ by the severity of reinfection and reinfecting variants were similar to the contemporaneous sequences circulating in the community. Patients with persistent COVID-19 demonstrated more rapid accumulation of sequence changes than seen with community-driven evolution with continued evolution during convalescent plasma or monoclonal antibody treatment. Conclusions Reinfecting SARS-CoV-2 viral genomes largely mirror contemporaneous circulating sequences in that geographic region, while persistent COVID-19 has been largely described in immunosuppressed individuals and is associated with accelerated viral evolution.

scholarly journals SARS-CoV-2 Sequence Characteristics of COVID-19 Persistence and Reinfection

2021 ◽  
Author(s):  
Manish Chandra Choudhary ◽  
Charles R Crain ◽  
Xueting Qiu ◽  
William Hanage ◽  
Jonathan Z. Li
Keyword(s):  
Amino Acid ◽  
Persistent Infection ◽  
Viral Evolution ◽  
Phylogenetic Reconstruction ◽  
Antibody Treatment ◽  
Systematic Assessment ◽  
Monoclonal Antibody Treatment ◽  
Viral Sequences ◽  
Sequence Characteristics ◽  
Baseline Health

Background. Both SARS-CoV-2 reinfection and persistent infection have been described, but a systematic assessment of mutations is needed. We assessed sequences from published cases of COVID-19 reinfection and persistence, characterizing the hallmarks of reinfecting sequences and the rate of viral evolution in persistent infection. Methods. A systematic review of PubMed was conducted to identify cases of SARS-CoV-2 reinfection and persistent infection with available sequences. Amino acid changes in the reinfecting sequence were compared to both the initial and contemporaneous community variants. Time-measured phylogenetic reconstruction was performed to compare intra-host viral evolution in persistent COVID-19 to community-driven evolution. Results. Fourteen reinfection and five persistent infection cases were identified. Reports of reinfection cases spanned a broad distribution of ages, baseline health status, reinfection severity, and occurred as early as 1.5 months or >8 months after the initial infection. The reinfecting viral sequences had a median of 9 amino acid changes with enrichment of changes in the S, ORF8 and N genes. The number of amino acid changes did not differ by the severity of reinfection and reinfecting variants were similar to the contemporaneous sequences circulating in the community. Patients with persistent COVID-19 demonstrated more rapid accumulation of mutations than seen with community-driven evolution with continued viral changes during convalescent plasma or monoclonal antibody treatment. Conclusions. SARS-CoV-2 reinfection does not require an unusual set of circumstances in the host or virus, while persistent COVID-19 is largely described in immunosuppressed individuals and is associated with accelerated viral evolution as measured by clock rates.

scholarly journals Nora virus, a persistent virus in Drosophila, defines a new picorna-like virus family

2006 ◽  
Vol 87 (10) ◽  
pp. 3045-3051 ◽  
Author(s):  
Mazen S. Habayeb ◽  
Sophia K. Ekengren ◽  
Dan Hultmark
Keyword(s):  
Persistent Infection ◽  
Open Reading Frames ◽  
Close Relative ◽  
Virus Family ◽  
Viral Genomes ◽  
Persistent Infections ◽  
New Family ◽  
Nora Virus ◽  
Persistent Virus ◽  
Viral Sequences

Several viruses, including picornaviruses, are known to establish persistent infections, but the mechanisms involved are poorly understood. Here, a novel picorna-like virus, Nora virus, which causes a persistent infection in Drosophila melanogaster, is described. It has a single-stranded, positive-sense genomic RNA of 11879 nt, followed by a poly(A) tail. Unlike other picorna-like viruses, the genome has four open reading frames (ORFs). One ORF encodes a picornavirus-like cassette of proteins for virus replication, including an iflavirus-like RNA-dependent RNA polymerase and a helicase that is related to those of mammalian picornaviruses. The three other ORFs are not closely related to any previously described viral sequences. The unusual sequence and genome organization in Nora virus suggest that it belongs to a new family of picorna-like viruses. Surprisingly, Nora virus could be detected in all tested D. melanogaster laboratory stocks, as well as in wild-caught material. The viral titres varied enormously, between 104 and 1010 viral genomes per fly in different stocks, without causing obvious pathological effects. The virus was also found in Drosophila simulans, a close relative of D. melanogaster, but not in more distantly related Drosophila species. It will now be possible to use Drosophila genetics to study the factors that control this persistent infection.

scholarly journals Rapid longitudinal SARS-CoV-2 intra-host emergence of novel haplotypes regardless of immune deficiencies

2021 ◽  
Author(s):  
Laura Manuto ◽  
Marco Grazioli ◽  
Andrea Spitaleri ◽  
Paolo Fontana ◽  
Luca Bianco ◽  
...  
Keyword(s):  
Viral Evolution ◽  
Viral Genomes ◽  
Network Analyses ◽  
Viral Spread ◽  
Minimum Spanning Network ◽  
Immune Deficiencies ◽  
Chinese Tourists ◽  
Containment Strategy ◽  
First Time ◽  
Viral Sequences

On February 2020, the municipality of Vo’, a small town near Padua (Italy), was quarantined due to the first coronavirus disease 19 (COVID-19)-related death detected in Italy. The entire population was swab tested in two sequential surveys. Here we report the analysis of the viral genomes, which revealed that the unique ancestor haplotype introduced in Vo’ belongs to lineage B and, more specifically, to the subtype found at the end of January 2020 in two Chinese tourists visiting Rome and other Italian cities, carrying mutations G11083T and G26144T. The sequences, obtained for 87 samples, allowed us to investigate viral evolution while being transmitted within and across households and the effectiveness of the non-pharmaceutical interventions implemented in Vo’. We report, for the first time, evidence that novel viral haplotypes can naturally arise intra-host within an interval as short as two weeks, in approximately 30% of the infected individuals, regardless of symptoms severity or immune system deficiencies. Moreover, both phylogenetic and minimum spanning network analyses converge on the hypothesis that the viral sequences evolved from a unique common ancestor haplotype, carried by an index case. The lockdown extinguished both viral spread and the emergence of new variants, confirming the efficiency of this containment strategy. The information gathered from household was used to reconstructs possible transmission events.

scholarly journals Divergent RNA Viruses In Macrophomina phaseolina exhibit potential as virocontrol agents

2020 ◽  
Author(s):  
Jing Wang ◽  
Yunxia Ni ◽  
Xintao Liu ◽  
Hui Zhao ◽  
Yannong Xiao ◽  
...  
Keyword(s):  
High Throughput Sequencing ◽  
Viral Evolution ◽  
Macrophomina Phaseolina ◽  
Phytopathogenic Fungus ◽  
Fungal Host ◽  
Viral Genomes ◽  
Geographical Regions ◽  
The Family ◽  
Viral Sequences ◽  
Complete Viral Genome

Abstract Macrophomina phaseolina is an important necrotrophic phytopathogenic fungus and cause extensive damage in many oilseed crops. Twelve M. phaseolina isolates with diverse biological phenotypes were selected for a high-throughput sequencing-based metatranscriptomic and bioinformatics analysis to identify viruses infecting M. phaseolina. The analysis identified 40 partial or nearly complete viral genome segments, 31 of which were novel viruses. Among these viral sequences, 43% of the viral genomes were double-stranded RNA (dsRNA), 47% were positive single-stranded RNA (ssRNA+), and the remaining 10% were negative sense-stranded RNA (ssRNA-). The 40 viruses showed affinity to 13 distinct viral lineages, including Bunyavirales (four viruses), Totiviridae (three viruses), Chrysoviridae (five viruses), Partitiviridae (four viruses), Hypoviridae (one virus), Endornaviridae (two viruses), Tombusviridae (three viruses), Narnaviridae (one virus), Potyviridae (one virus), Bromoviridae (one virus), Virgaviridae (six viruses), “Fusagraviridae” (five viruses), and Ourmiavirus (four viruses). Two viruses are closely related to two families, Potyviridae and Bromoviridae, which previously contained no mycovirus species. Moreover, nine novel viruses associated with M. phaseolina were identified in the family Totiviridae, Endornaviridae, and Partitiviridae. Coinfection with multiple viruses is prevalent in M. phaseolina, with each isolate harboring different numbers of viruses, ranging from three to eighteen. Furthermore, the effects of the viruses on the fungal host were analyzed according to the biological characteristics of each isolate. The results suggested that Macrophomina phaseolina hypovirus 2, Macrophomina phaseolina fusagravirus virus 1-5 (MpFV1-5), Macrophomina phaseolina endornavirus 1-2 (MpEV1-2), Macrophomina phaseolina ourmia-like virus 1-3 (MpOLV1-3), Macrophomina phaseolina mitovirus 4 (MpMV4), and Macrophomina phaseolina mycobunyavirus 1-4 (MpMBV1-4) were only detected in hypovirulent isolates. Those viruses associated with hypovirulence might be used as biological control agents as an environmentally friendly alternative to chemical fungicides. These findings considerably expand our understanding of mycoviruses in M. phaseolina and unvailed the presence of a huge difference among viruses in isolates from different hosts in distant geographical regions. Together, the present study provides new knowledge about viral evolution and fungus-virus coevolution.

scholarly journals Acquisition and onward transmission of a SARS-CoV-2 E484K variant among household contacts of a bamlanivimab-treated patient

2021 ◽  
Author(s):  
Arick P Sabin ◽  
Craig S Richmond ◽  
Paraic A Kenny
Keyword(s):  
Monoclonal Antibody ◽  
De Novo ◽  
Treated Patient ◽  
Viral Evolution ◽  
Surveillance Program ◽  
Antibody Treatment ◽  
Selective Pressures ◽  
Real Risk ◽  
Monoclonal Antibody Treatment ◽  
Close Contacts

The implementation of monoclonal antibody therapeutics during the COVID19 pandemic has altered the selective pressures encountered by SARS-CoV-2, raising the possibility of selection for variants resistant to one or more monoclonal antibodies and subsequent transmission into the wider population. Early studies indicated that monoclonal antibody treatment in immunocompromised individuals could result in within-host viral evolution preferentially affecting epitopes recognized by these antibodies, although whether this signifies a real risk of transmissible antibody resistant virus is unclear. In this study we have taken advantage of a regional SARS-CoV-2 genomic surveillance program encompassing regions in Wisconsin, Minnesota and Iowa to monitor the introduction or de novo emergence of SARS-Cov-2 lineages with clinically relevant variants. Here we describe a newly acquired E484K mutation in the SARS-CoV-2 spike protein detected within the B.1.311 lineage. Multiple individuals in two related households were infected. The timing and patterns of subsequent spread were consistent with de novo emergence of this E484K variant in the initially affected individual who had been treated with bamlanivimab monotherapy. The subsequent transmission to close contacts occurred several days after the resolution of symptoms and the end of this patient's quarantine period. Our study suggest that the selective pressures introduced by the now widespread administration of these antibodies may warrant increased genomic surveillance to identify and mitigate spread of therapy-induced variants.

Integration of viral DNA sequences in cells transformed by adenovirus 2 or SV40

1980 ◽  
Vol 210 (1180) ◽  
pp. 423-435 ◽  
Keyword(s):  
Cell Lines ◽  
Dna Sequences ◽  
Viral Genome ◽  
Viral Dna ◽  
Viral Genomes ◽  
Viral Dnas ◽  
Cellular Dna ◽  
Viral Insertion ◽  
Viral Sequences ◽  
Heteroduplex Formation

We have cloned and propagated in prokaryotic vectors the viral DNA sequences that are integrated in a variety of cells transformed by adenovirus 2 or SV40. Analysis of the clones reveals that the viral DNA sequences sometimes are arranged in a simple fashion, collinear with the viral genome; in other cell lines there are complex arrangements of viral sequences in which tracts of the viral genome are inverted with respect to each other. In several cases the nucleotide sequences at the joints between cell and viral sequences have been determined: usually there is a sharp transition between cellular and viral DNAs. The viral sequences are integrated at different locations within the genomes of different cell lines; likewise there is no specific site on the viral genomes at which integration occurs. Sometimes the viral sequences are integrated within repetitive cellular DNA, and sometimes within unique sequences. In some cases there is evidence that the viral sequences along with the flanking cell DNA have been amplified after integration. The sequences that flank the viral insertion in the line of SV40-transformed rat cells known as 14B have been used as probes to isolate, from untransformed rat cells, clones that carry the region of the chromosome in which integration occurred. Analysis of the structure of these clones by restriction endonuclease digestion and heteroduplex formation shows that a rearrangement of cellular sequences has occurred, presumably as a consequence of integration.

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