|
Phylogenetic network analysis of SARS-CoV-2 genomes
This is a phylogenetic network of SARS-CoV-2 genomes sampled from across the world. These genomes are closely related and under evolutionary selection in their human hosts, sometimes with parallel evolution events, that is, the same virus mutation emerges in two different human hosts. This makes character-based phylogenetic networks the method of choice for reconstructing their evolutionary paths and their ancestral genome in the human host. The network method has been used in around 10,000 phylogenetic studies of diverse organisms, and is mostly known for reconstructing the prehistoric population movements of humans and for ecological studies, but is less commonly employed in the field of virology.
|
HCoV-EMC/2012 Genomic Characterization of a Newly Discovered Coronavirus Associated with Acute Respiratory Distress Syndrome in Humans
A novel human coronavirus (HCoV-EMC/2012) was isolated from a man with acute pneumonia and renal failure in June 2012. This report describes the complete genome sequence, genome organization, and expression strategy of HCoV-EMC/2012 and its relation with known coronaviruses. The genome contains 30,119 nucleotides and contains at least 10 predicted open reading frames, 9 of which are predicted to be expressed from a nested set of seven subgenomic mRNAs. Phylogenetic analysis of the replicase gene of coronaviruses with completely sequenced genomes showed that HCoV-EMC/2012 is most closely related to Tylonycteris bat coronavirus HKU4 (BtCoV-HKU4) and Pipistrellus bat coronavirus HKU5 (BtCoV-HKU5), which prototype two species in lineage C of the genus Betacoronavirus. In accordance with the guidelines of the International Committee on Taxonomy of Viruses, and in view of the 75% and 77% amino acid sequence identity in 7 conserved replicase domains with BtCoV-HKU4 and BtCoV-HKU5, respectively, we propose that HCoV-EMC/2012 prototypes a novel species in the genus Betacoronavirus. HCoV-EMC/2012 may be most closely related to a coronavirus detected in Pipistrellus pipistrellus in The Netherlands, but because only a short sequence from the most conserved part of the RNA-dependent RNA polymerase-encoding region of the genome was reported for this bat virus, its genetic distance from HCoV-EMC remains uncertain. HCoV-EMC/2012 is the sixth coronavirus known to infect humans and the first human virus within betacoronavirus lineage C.
|
Genetic tracing 'barcode' is rapidly revealing COVID-19's journey and evolution
Their preliminary analysis, using information from a global database of genetic information gleaned from coronavirus testing, suggests that there are at least six to 10 slightly different versions of the virus infecting people in America, some of which are either the same as, or have subsequently evolved from, strains directly from Asia, while others are the same as those found in Europe.
|
Bat SARS-like coronavirus WIV1 encodes an extra accessory protein ORFX
2 involved in modulation of host immune response
Bats harbor severe acute respiratory syndrome-like coronaviruses (SL-CoVs) from
which the causative agent of the 2002-3 SARS pandemic is thought to have originated.
However, despite a large number of genetically diverse SL-CoV sequences detected
in bats, only two strains (named WIV1 and WIV16) have been successfully cultured
in vitro. These two strains differ from SARS-CoV only in containing an extra ORF
(named ORFX) between ORF6 and ORF7 with no homology to any known protein
sequences. In this study, we constructed a full-length cDNA clone of SL-CoV WIV1
(rWIV1), an ORFX deletion mutant (rWIV1-ΔX), and a GFP-expressing mutant
(rWIV1-GFP-ΔX). Northern blot and fluorescent microscopy indicate that ORFX was
expressed during WIV1 infection. Virus infection assay showed that rWIV1-ΔX
replicated as efficiently as rWIV1 in Vero E6, Calu-3, and HeLa-hACE2 cells.
Further study showed that ORFX could inhibit interferon production and activates
NF-κB. Our results demonstrate for the first time that the unique ORFX in the WIV1
strain is a functional gene involving modulation of host immune response, but not
essential for in vitro viral replication.
|
|
|
|
Complete Genome Sequence of a 2019 Novel Coronavirus (SARS-CoV-2) Strain Isolated in Nepal
A complete genome sequence was obtained for a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain isolated from an oropharyngeal swab specimen of a Nepalese patient with coronavirus disease 2019 (COVID-19), who had returned to Nepal after traveling to Wuhan, China.
|
|
Pathogenic priming likely contributes to serious and critical illness and mortality in COVID-19 via autoimmunity
• All SARS-CoV-2 immunogenic epitopes have similarity to human proteins except one.
• Roughly one-third of the potentially targeted human proteins (putative autoantigens) are key players in the adaptive immune system.
• The list of viral/human protein matches provides clues on which epitopes or parts of epitopes might be involved in the immunopathogenesis of COVID-19 disease from SARS-CoV-2 infection.
• It also indicates which epitopes might be responsible for autoimmunological pathogenic priming due to prior infection or following exposure to SARS-CoV-2 or relatives following vaccination.
• These epitopes should be excluded from vaccines under development to minimize autoimmunity due to risk of pathogenic priming
|
|
Spike mutation pipeline reveals the emergence of a more transmissible form of SARS-CoV-2
We have developed an analysis pipeline to facilitate real-time mutation tracking in SARS-CoV-2,
focusing initially on the Spike (S) protein because it mediates infection of human cells and is the
target of most vaccine strategies and antibody-based therapeutics. To date we have identified
fourteen mutations in Spike that are accumulating. Mutations are considered in a broader
phylogenetic context, geographically, and over time, to provide an early warning system to
reveal mutations that may confer selective advantages in transmission or resistance to
interventions. Each one is evaluated for evidence of positive selection, and the implications of
the mutation are explored through structural modeling. The mutation Spike D614G is of urgent
concern; it began spreading in Europe in early February, and when introduced to new regions it
rapidly becomes the dominant form. Also, we present evidence of recombination between
locally circulating strains, indicative of multiple strain infections. These finding have important
implications for SARS-CoV-2 transmission, pathogenesis and immune interventions
|
|
NYT: Corum and Zimmer - How Coronavirus Mutates and Spreads
|
|
|
