virology blog
About viruses and viral disease
In this special episode, Dr. Griffin answers questions about the recent cases of monkeypox including their origin, clinical presentation, diagnosis, treatment, and overall risk.
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TWiV explains a study of how climate change is predicted to increase cross-species viral transmission risk, and increased memory B cell potency and breadth after a SARS-CoV-2 mRNA vaccine boost.
Hosts: Vincent Racaniello, Dickson Despommier, and Amy Rosenfeld
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Elke, Adam, and Gabor join TWiV to discuss their work on Lloviu virus, a filovirus, including recovery of infectious virus from a DNA copy of the genome and from Schreiber’s bats in Hungary.
Hosts: Vincent Racaniello, Rich Condit, Kathy Spindler, and Brianne Barker
Guests: Elke Muhlberger, Adam Hume, and Gabor Kemenesi
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Download TWiV 891 (65 MB .mp3, 108 min)
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TWiV discusses the virome of game animals in China, and the finding that binding of sarbecoviruses to ACE2 is an ancestral and evolvable trait.
Hosts: Vincent Racaniello, Dickson Despommier, and Amy Rosenfeld
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Download TWiV 875 (128 MB .mp3, 107 min)
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All human viruses, including SARS-CoV-2, arose from spillovers from other animals. Results of a recent study of bat samples collected in a small region of Yunnan Province, China revealed additional close relatives of SARS-CoV-2 and SARS-CoV.
After the identification of SARS-CoV-2 in early 2020, wildlife sampling and retrospective genome sequencing revealed highly related viruses in animals. The virus RaTG13, from Rhinolophus affinis, shares the highest overall genome identity with SARS-CoV-2, 96.10%. The virus RmYN02 from the bat R. malayanus is the closest relative of SARS-CoV-2 in the ORF1ab open reading frame. Pangolin viruses from Guangdong have identical amino acids at six key residues in the receptor binding domain (RBD) needed for binding to human ACE2. A more distantly related coronavirus was isolated from a bat in Japan, and two viruses from Cambodia have 92.6% genome identity with SARS-CoV-2 and share five of six critical amino acids in the RBD. Finally a bat coronavirus from Thailand is closely related to RmYN02. These observations demonstrate that bats from a broad part of Asia harbor close relatives of SARS-CoV-2.
Fecal samples, oral swabs, and urine samples collected from mainly horseshoe bats in a small area of Yunnan Province between May 2019 – November 2020 were analyzed by RNA sequencing. The results revealed 9 novel betacoronaviruses and 17 alphacoronaviruses. Four of the betacoronaviruses were related to SARS-CoV-2 and three were related to SARS-CoV. Rhinolophus pusillus virus RpYN06 was the closest relative of SARS-CoV-2 in most of the genome with the exception of the spike gene. The other three SARS-CoV-2 related coronaviruses encode a spike gene that could weakly bind to the hACE2 receptor in vitro. Patches of high sequence identity in different regions of the genome illustrate the work of extensive recombination events.
While all the viruses identified in this study, as well as the previously discovered RmYN01 and RmYN02, were identified in a 1100 hectare part of Yunnan province, the results of ecological modeling show that many species of rhinolophid bats are present in much of Southeast Asia and southern China. Numerous other bat species and other wildlife inhabit this area, many of which can be infected by SARS-CoV-2. Hence much more wildlife sampling is needed to track potential spillovers of viruses into humans.
These findings also demonstrate that a very large part of Asia might harbor the direct ancestor of SARS-CoV-2. Remember that HIV/AIDS was first detected in Los Angeles in 1981 but the virus spilled over from a chimpanzee to a human in Africa in ~1920.
The seven human coronaviruses have all originated from spillover events from a variety of nonhuman animals, including bats, rodents, and camels. Recently isolated coronaviruses from humans appear to have originated in pigs and dogs.
Three of 369 plasma samples collected between May 2014 and December 2015 in two schools in Haiti were found to be positive for coronavirus. All three children had fever, and one reported cough and abdominal pain. Whole genome sequence analysis of all three isolates revealed them to be porcine deltacoronaviruses (PDCoV). The human coronaviruses known to date are alpha- and betacoronaviruses.
PDCoV was first identified in 2012 in Hong Kong and then in 2014 in the Americas. The virus infects epithelial cells in the jejunum and ileum and the large intestine, leading to gastrointestinal symptoms. No PDCoV infections have been reported in Haitian domestic pigs.
The PDCoVs isolated four months apart from two children attending the same school are closely related to a virus isolated from pigs a year later in China. The other Haitian child was infected with PDCoV that is more closely related to an isolate from pigs in Arkansas from 2015. The implication of sequence analysis is that two separate zoonotic transmissions took place. How the viruses traveled from the US and China to Haiti is not clear.
All three PDCoV human isolates share a signature of amino acid changes in the viral ORF1a/b and spike proteins that is not seen in other PDCoV isolates. These changes might have been selected during reproduction in human hosts.
In a separate study, 8 of 301 nasopharyngeal swabs from patients hospitalized between 2017-2018 with pneumonia in Malaysia were shown to harbor canine coronavirus (CCoV), an alpha coronavirus. Close analysis of the genome sequence revealed that the virus is a recombinant, with most of the genome originating from CCoV and part of the spike from feline coronavirus.
Canine and feline coronaviruses cause moderate to severe intestinal disease in dogs and cats. The viruses have a worldwide distribution and given the prevalence of these animals as pets, it is not surprising that human infections may occur, albeit rarely. The eight patients who harbored this novel CoV were children living in areas where exposure to domestic animal and jungle wildlife would be expected, possibly explaining how the infections were acquired.
These human infections with porcine and canine coronaviruses appear to be isolated incidents which did not lead to extensive human transmission. Nevertheless the findings emphasize the public health threat of animal coronaviruses and the need for improving our surveillance for these viruses.