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Article ; Online: A palindromic RNA sequence as a common breakpoint contributor to copy-choice recombination in SARS-COV-2.

Gallaher, William R

2020 Volume 165, Issue 10, Page(s) 2341–2348

Abstract: Much remains unknown concerning the origin of the novel pandemic coronavirus that has raged across the globe since emerging in Wuhan of Hubei province, near the center of the People's Republic of China, in December of 2019. All current members of the ... ...

Abstract	Much remains unknown concerning the origin of the novel pandemic coronavirus that has raged across the globe since emerging in Wuhan of Hubei province, near the center of the People's Republic of China, in December of 2019. All current members of the family Coronaviridae have arisen by a combination of incremental adaptive mutations, against the backdrop of many recombinational events throughout the past, rendering each a unique mosaic of RNA sequences from diverse sources. The consensus among virologists is that the base sequence of the novel coronavirus, designated SARS-CoV-2, was derived from a common ancestor of a bat coronavirus, represented by the strain RaTG13, isolated in Yunnan province in 2013. Into that ancestral genetic background, several recombination events have since occurred from other divergent bat-derived coronaviruses, resulting in localized discordance between the two. One such event left SARS-CoV-2 with a receptor binding domain (RBD) capable of binding the human ACE-2 receptor lacking in RaTG13, and a second event uniquely added to SARS-CoV-2 a site specific for furin, capable of efficient endoproteolytic cleavage and activation of the spike glycoprotein responsible for virus entry and cell fusion. This paper demonstrates by bioinformatic analysis that such recombinational events are facilitated by short oligonucleotide "breakpoint sequences", similar to CAGAC, that direct recombination naturally to certain positions in the genome at the boundaries between blocks of RNA code and potentially RNA structure. This "breakpoint sequence hypothesis" provides a natural explanation for the biogenesis of SARS-CoV-2 over time and in the wild.
MeSH term(s)	Amino Acid Sequence ; Animals ; Base Sequence ; Betacoronavirus/classification ; Betacoronavirus/genetics ; COVID-19 ; China/epidemiology ; Chiroptera/virology ; Coronaviridae/classification ; Coronaviridae/genetics ; Coronavirus Infections/epidemiology ; Coronavirus Infections/virology ; Evolution, Molecular ; Genome, Viral ; Host Microbial Interactions/genetics ; Humans ; Inverted Repeat Sequences ; Pandemics ; Phylogeny ; Pneumonia, Viral/epidemiology ; Pneumonia, Viral/virology ; RNA, Viral/genetics ; Recombination, Genetic ; SARS-CoV-2 ; Sequence Alignment
Chemical Substances	RNA, Viral
Keywords	covid19
Language	English
Publishing date	2020-07-31
Publishing country	Austria
Document type	Journal Article
ZDB-ID	7491-3
ISSN	1432-8798 ; 0304-8608
ISSN (online)	1432-8798
ISSN	0304-8608
DOI	10.1007/s00705-020-04750-z
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Article: A palindromic RNA sequence as a common breakpoint contributor to copy-choice recombination in SARS-COV-2

Gallaher, William R

Archives of virology. 2020 Oct., v. 165, no. 10

2020

Abstract: Much remains unknown concerning the origin of the novel pandemic coronavirus that has raged across the globe since emerging in Wuhan of Hubei province, near the center of the People’s Republic of China, in December of 2019. All current members of the ... ...

Abstract	Much remains unknown concerning the origin of the novel pandemic coronavirus that has raged across the globe since emerging in Wuhan of Hubei province, near the center of the People’s Republic of China, in December of 2019. All current members of the family Coronaviridae have arisen by a combination of incremental adaptive mutations, against the backdrop of many recombinational events throughout the past, rendering each a unique mosaic of RNA sequences from diverse sources. The consensus among virologists is that the base sequence of the novel coronavirus, designated SARS-CoV-2, was derived from a common ancestor of a bat coronavirus, represented by the strain RaTG13, isolated in Yunnan province in 2013. Into that ancestral genetic background, several recombination events have since occurred from other divergent bat-derived coronaviruses, resulting in localized discordance between the two. One such event left SARS-CoV-2 with a receptor binding domain (RBD) capable of binding the human ACE-2 receptor lacking in RaTG13, and a second event uniquely added to SARS-CoV-2 a site specific for furin, capable of efficient endoproteolytic cleavage and activation of the spike glycoprotein responsible for virus entry and cell fusion. This paper demonstrates by bioinformatic analysis that such recombinational events are facilitated by short oligonucleotide “breakpoint sequences”, similar to CAGAC, that direct recombination naturally to certain positions in the genome at the boundaries between blocks of RNA code and potentially RNA structure. This “breakpoint sequence hypothesis” provides a natural explanation for the biogenesis of SARS-CoV-2 over time and in the wild.
Keywords	Chiroptera ; RNA ; Severe acute respiratory syndrome coronavirus 2 ; ancestry ; biogenesis ; bioinformatics ; cell fusion ; genetic background ; genome ; glycoproteins ; humans ; nucleotide sequences ; oligonucleotides ; pandemic ; virology ; viruses ; China
Language	English
Dates of publication	2020-10
Size	p. 2341-2348.
Publishing place	Springer Vienna
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	7491-3
ISSN	1432-8798 ; 0304-8608
ISSN (online)	1432-8798
ISSN	0304-8608
DOI	10.1007/s00705-020-04750-z
Database	NAL-Catalogue (AGRICOLA)

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Article: A palindromic RNA sequence as a common breakpoint contributor to copy-choice recombination in SARS-COV-2

Gallaher, William R

Arch Virol

Abstract	Much remains unknown concerning the origin of the novel pandemic coronavirus that has raged across the globe since emerging in Wuhan of Hubei province, near the center of the People's Republic of China, in December of 2019. All current members of the family Coronaviridae have arisen by a combination of incremental adaptive mutations, against the backdrop of many recombinational events throughout the past, rendering each a unique mosaic of RNA sequences from diverse sources. The consensus among virologists is that the base sequence of the novel coronavirus, designated SARS-CoV-2, was derived from a common ancestor of a bat coronavirus, represented by the strain RaTG13, isolated in Yunnan province in 2013. Into that ancestral genetic background, several recombination events have since occurred from other divergent bat-derived coronaviruses, resulting in localized discordance between the two. One such event left SARS-CoV-2 with a receptor binding domain (RBD) capable of binding the human ACE-2 receptor lacking in RaTG13, and a second event uniquely added to SARS-CoV-2 a site specific for furin, capable of efficient endoproteolytic cleavage and activation of the spike glycoprotein responsible for virus entry and cell fusion. This paper demonstrates by bioinformatic analysis that such recombinational events are facilitated by short oligonucleotide "breakpoint sequences", similar to CAGAC, that direct recombination naturally to certain positions in the genome at the boundaries between blocks of RNA code and potentially RNA structure. This "breakpoint sequence hypothesis" provides a natural explanation for the biogenesis of SARS-CoV-2 over time and in the wild.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #690501
Database	COVID19

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Article ; Online: Modeling of the Ebola virus delta peptide reveals a potential lytic sequence motif.

Gallaher, William R / Garry, Robert F

Viruses

2015 Volume 7, Issue 1, Page(s) 285–305

Abstract: Filoviruses, such as Ebola and Marburg viruses, cause severe outbreaks of human infection, including the extensive epidemic of Ebola virus disease (EVD) in West Africa in 2014. In the course of examining mutations in the glycoprotein gene associated with ...

Abstract	Filoviruses, such as Ebola and Marburg viruses, cause severe outbreaks of human infection, including the extensive epidemic of Ebola virus disease (EVD) in West Africa in 2014. In the course of examining mutations in the glycoprotein gene associated with 2014 Ebola virus (EBOV) sequences, a differential level of conservation was noted between the soluble form of glycoprotein (sGP) and the full length glycoprotein (GP), which are both encoded by the GP gene via RNA editing. In the region of the proteins encoded after the RNA editing site sGP was more conserved than the overlapping region of GP when compared to a distant outlier species, Tai Forest ebolavirus. Half of the amino acids comprising the "delta peptide", a 40 amino acid carboxy-terminal fragment of sGP, were identical between otherwise widely divergent species. A lysine-rich amphipathic peptide motif was noted at the carboxyl terminus of delta peptide with high structural relatedness to the cytolytic peptide of the non-structural protein 4 (NSP4) of rotavirus. EBOV delta peptide is a candidate viroporin, a cationic pore-forming peptide, and may contribute to EBOV pathogenesis.
MeSH term(s)	Amino Acid Motifs ; Amino Acid Sequence ; Conserved Sequence ; Ebolavirus/genetics ; Genetic Variation ; Lysine/chemistry ; Lysine/genetics ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; Sequence Alignment ; Viral Envelope Proteins/chemistry ; Viral Envelope Proteins/genetics
Chemical Substances	Viral Envelope Proteins ; envelope glycoprotein, Ebola virus ; Lysine (K3Z4F929H6)
Language	English
Publishing date	2015-01-20
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v7010285
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Article ; Online: Ebola virus delta peptide is an enterotoxin.

Melnik, Lilia I / Guha, Shantanu / Ghimire, Jenisha / Smither, Allison R / Beddingfield, Brandon J / Hoffmann, Andrew R / Sun, Leisheng / Ungerleider, Nathan A / Baddoo, Melody C / Flemington, Erik K / Gallaher, William R / Wimley, William C / Garry, Robert F

Cell reports

2022 Volume 38, Issue 1, Page(s) 110172

Abstract: During the 2013-2016 West African (WA) Ebola virus (EBOV) outbreak, severe gastrointestinal symptoms were common in patients and associated with poor outcome. Delta peptide is a conserved product of post-translational processing of the abundant EBOV ... ...

Abstract	During the 2013-2016 West African (WA) Ebola virus (EBOV) outbreak, severe gastrointestinal symptoms were common in patients and associated with poor outcome. Delta peptide is a conserved product of post-translational processing of the abundant EBOV soluble glycoprotein (sGP). The murine ligated ileal loop model was used to demonstrate that delta peptide is a potent enterotoxin. Dramatic intestinal fluid accumulation follows injection of biologically relevant amounts of delta peptide into ileal loops, along with gross alteration of villous architecture and loss of goblet cells. Transcriptomic analyses show that delta peptide triggers damage response and cell survival pathways and downregulates expression of transporters and exchangers. Induction of diarrhea by delta peptide occurs via cellular damage and regulation of genes that encode proteins involved in fluid secretion. While distinct differences exist between the ileal loop murine model and EBOV infection in humans, these results suggest that delta peptide may contribute to EBOV-induced gastrointestinal pathology.
MeSH term(s)	Animals ; Diarrhea/virology ; Ebolavirus/metabolism ; Enterotoxins/toxicity ; Female ; Gastroenteritis/pathology ; Gastroenteritis/virology ; Hemorrhagic Fever, Ebola/pathology ; Male ; Mice ; Mice, Inbred BALB C ; Viral Envelope Proteins/toxicity
Chemical Substances	Enterotoxins ; Viral Envelope Proteins
Language	English
Publishing date	2022-01-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2021.110172
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Article ; Online: Towards a sane and rational approach to management of Influenza H1N1 2009.

Gallaher, William R

Virology journal

2009 Volume 6, Page(s) 51

Abstract: Beginning in March 2009, an outbreak of influenza in North America was found to be caused by a new strain of influenza virus, designated Influenza H1N1 2009, which is a reassortant of swine, avian and human influenza viruses. Over a thousand total cases ... ...

Abstract	Beginning in March 2009, an outbreak of influenza in North America was found to be caused by a new strain of influenza virus, designated Influenza H1N1 2009, which is a reassortant of swine, avian and human influenza viruses. Over a thousand total cases were identified with the first month, chiefly in the United States and Mexico, but also involving several European countries. Actions concerning Influenza H1N1 2009 need to be based on fact and science, following recommendations of public health officials, and not fueled by political, legal or other interests. Every influenza outbreak or pandemic is unique, so the facts of each one must be studied before an appropriate response can be developed. While reports are preliminary, through the first 4 weeks of the outbreak it does not appear to be severe either in terms of the attack rate in communities or in the virulence of the virus itself. However, there are significant changes in both the hemagglutinin and neuraminidase proteins of the new virus, 27.2% and 18.2% of the amino acid sequence, from prior H1N1 isolates in 2008 and the current vaccine. Such a degree of change qualifies as an "antigenic shift", even while the virus remains in the H1N1 family of influenza viruses, and may give influenza H1N1 2009 significant pandemic potential. Perhaps balancing this shift, the novel virus retains more of the core influenza proteins from animal strains than successful human influenza viruses, and may be inhibited from its maximum potential until further reassortment or mutation better adapts it to multiplication in humans. While contact and respiratory precautions such as frequent handwashing will slow the virus through the human population, it is likely that development of a new influenza vaccine tailored to this novel Influenza H1N1 2009 strain will be essential to blunt its ultimate pandemic impact.
MeSH term(s)	Disease Outbreaks/prevention & control ; Humans ; Influenza A Virus, H1N1 Subtype/genetics ; Influenza A Virus, H1N1 Subtype/immunology ; Influenza A Virus, H1N1 Subtype/isolation & purification ; Influenza Vaccines/immunology ; Influenza, Human/epidemiology ; Influenza, Human/prevention & control ; Influenza, Human/virology
Chemical Substances	Influenza Vaccines
Language	English
Publishing date	2009-05-07
Publishing country	England
Document type	Editorial ; Review
ISSN	1743-422X
ISSN (online)	1743-422X
DOI	10.1186/1743-422X-6-51
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Article ; Online: Comparison of short- and long-term exposure effects of cruciferous and apiaceous vegetables on carcinogen metabolizing enzymes in Wistar rats.

Kim, Jae Kyeom / Strapazzon, Noemia / Gallaher, Cynthia M / Stoll, Dwight R / Thomas, William / Gallaher, Daniel D / Trudo, Sabrina P

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association

2017 Volume 108, Issue Pt A, Page(s) 194–202

Abstract: Cruciferous and apiaceous vegetables may be chemopreventive due to their ability to modulate carcinogen-metabolizing enzymes but whether the effects on such enzymes are sustained over time is unknown. To examine the short- and long-term effects of the ... ...

Abstract	Cruciferous and apiaceous vegetables may be chemopreventive due to their ability to modulate carcinogen-metabolizing enzymes but whether the effects on such enzymes are sustained over time is unknown. To examine the short- and long-term effects of the vegetables, rats were fed one of four diets for 7, 30, or 60 d: AIN-93G, CRU (21% cruciferous vegetables-fresh broccoli, green cabbage, watercress), API (9% apiaceous vegetables - fresh parsnips, celery), or API + CRU (10.5% CRU + 4.5% API). Although CRU increased activity and protein expression of cytochrome P450 (CYP) 1A1 and CYP1A2 after 7 d, only activity was sustained after 30 and 60 d. There was a trend towards an interaction between the length of feeding period and CRU for CYP1A1 activity; activity increased with greater time of feeding. API increased CYP1A2 activity but decreased sulfotransferase 1A1 activity after 7 d, although not at later times. Altogether, increased CYP1A activity by CRU was maintained with long term feeding while protein amount decreased, suggesting influence by mechanisms other than, or in addition to, transcriptional regulation. Thus, response patterns and interactions with length of feeding may differ, depending upon the types of vegetables and enzymes, requiring caution when interpreting the results of short-term feeding studies.
Language	English
Publishing date	2017-10
Publishing country	England
Document type	Journal Article
ZDB-ID	782617-5
ISSN	1873-6351 ; 0278-6915
ISSN (online)	1873-6351
ISSN	0278-6915
DOI	10.1016/j.fct.2017.07.057
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Article ; Online: Towards a sane and rational approach to management of Influenza H1N1 2009

Gallaher William R

Virology Journal, Vol 6, Iss 1, p

2009 Volume 51

Abstract: Abstract Beginning in March 2009, an outbreak of influenza in North America was found to be caused by a new strain of influenza virus, designated Influenza H1N1 2009, which is a reassortant of swine, avian and human influenza viruses. Over a thousand ... ...

Abstract	Abstract Beginning in March 2009, an outbreak of influenza in North America was found to be caused by a new strain of influenza virus, designated Influenza H1N1 2009, which is a reassortant of swine, avian and human influenza viruses. Over a thousand total cases were identified with the first month, chiefly in the United States and Mexico, but also involving several European countries. Actions concerning Influenza H1N1 2009 need to be based on fact and science, following recommendations of public health officials, and not fueled by political, legal or other interests. Every influenza outbreak or pandemic is unique, so the facts of each one must be studied before an appropriate response can be developed. While reports are preliminary, through the first 4 weeks of the outbreak it does not appear to be severe either in terms of the attack rate in communities or in the virulence of the virus itself. However, there are significant changes in both the hemagglutinin and neuraminidase proteins of the new virus, 27.2% and 18.2% of the amino acid sequence, from prior H1N1 isolates in 2008 and the current vaccine. Such a degree of change qualifies as an "antigenic shift", even while the virus remains in the H1N1 family of influenza viruses, and may give influenza H1N1 2009 significant pandemic potential. Perhaps balancing this shift, the novel virus retains more of the core influenza proteins from animal strains than successful human influenza viruses, and may be inhibited from its maximum potential until further reassortment or mutation better adapts it to multiplication in humans. While contact and respiratory precautions such as frequent handwashing will slow the virus through the human population, it is likely that development of a new influenza vaccine tailored to this novel Influenza H1N1 2009 strain will be essential to blunt its ultimate pandemic impact.
Keywords	Microbiology ; QR1-502 ; Science ; Q ; DOAJ:Microbiology ; DOAJ:Biology ; DOAJ:Biology and Life Sciences ; Medicine (General) ; R5-920 ; Medicine ; R ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Subject code	306
Language	English
Publishing date	2009-05-01T00:00:00Z
Publisher	BioMed Central
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Modeling of the Ebola Virus Delta Peptide Reveals a Potential Lytic Sequence Motif

William R. Gallaher / Robert F. Garry

Viruses, Vol 7, Iss 1, Pp 285-

2015 Volume 305

Abstract	Filoviruses, such as Ebola and Marburg viruses, cause severe outbreaks of human infection, including the extensive epidemic of Ebola virus disease (EVD) in West Africa in 2014. In the course of examining mutations in the glycoprotein gene associated with 2014 Ebola virus (EBOV) sequences, a differential level of conservation was noted between the soluble form of glycoprotein (sGP) and the full length glycoprotein (GP), which are both encoded by the GP gene via RNA editing. In the region of the proteins encoded after the RNA editing site sGP was more conserved than the overlapping region of GP when compared to a distant outlier species, Tai Forest ebolavirus. Half of the amino acids comprising the “delta peptide”, a 40 amino acid carboxy-terminal fragment of sGP, were identical between otherwise widely divergent species. A lysine-rich amphipathic peptide motif was noted at the carboxyl terminus of delta peptide with high structural relatedness to the cytolytic peptide of the non-structural protein 4 (NSP4) of rotavirus. EBOV delta peptide is a candidate viroporin, a cationic pore-forming peptide, and may contribute to EBOV pathogenesis.
Keywords	Ebola ; ebolavirus ; filovirus ; lysin ; viroporin ; enterotoxin ; ion channel ; Microbiology ; QR1-502 ; Science ; Q
Language	English
Publishing date	2015-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Changing Attitudes toward the COVID-19 Vaccine among North Carolina Participants in the COVID-19 Community Research Partnership.

Enwezor, Chukwunyelu H / Peacock, James E / Seals, Austin L / Edelstein, Sharon L / Hinkelman, Amy N / Wierzba, Thomas F / Munawar, Iqra / Maguire, Patrick D / Lagarde, William H / Runyon, Michael S / Gibbs, Michael A / Gallaher, Thomas R / Sanders, John W / Herrington, David M

Vaccines

2021 Volume 9, Issue 8

Abstract: Coronavirus Disease-2019 (COVID-19) vaccine acceptance is variable. We surveyed participants in the COVID-19 Community Research Partnership from 17 December 2020 to 13 January 2021 to assess vaccine receptiveness. Vaccine uptake was then monitored until ... ...

Abstract	Coronavirus Disease-2019 (COVID-19) vaccine acceptance is variable. We surveyed participants in the COVID-19 Community Research Partnership from 17 December 2020 to 13 January 2021 to assess vaccine receptiveness. Vaccine uptake was then monitored until 15 May 2021; 20,232 participants responded to the receptiveness survey with vaccination status accessed in 18,874 participants via daily follow-up surveys (participants not completing daily surveys ≥30 days to 15 May 2021, were excluded). In the initial survey, 4802 (23.8%) were vaccine hesitant. Hesitancy was most apparent in women (Adjusted RR 0.93,
Language	English
Publishing date	2021-08-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines9080916
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