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swine

We missed SARS-CoV-2, what other coronaviruses are we ignoring?

15 October 2020 by Vincent Racaniello

pig

After SARS-Cov came and went in 2003, we learned that bats in China harbor SARS-like coronaviruses with the capacity to infect human cells. This information was largely ignored, otherwise we would have stopped this pandemic in its tracks. A coronavirus that went from bats to pigs might represent yet another threat to human health.

Swine acute diarrhea syndrome coronavirus (SADS-CoV) has caused outbreaks of lethal disease in piglets throughout China. This virus likely spilled over from Rhinolophus species bats into pigs in China. The swine industry in China is extensive and there are many opportunities for contact between humans and pigs, raising the question of whether SADS-CoV might infect humans.

To address this question, a variety of cells in culture were assessed for susceptibility and permissivity to SADS-CoV. Production of infectious virus was observed after infection of swine , primate, cat and human cell lines. Primary human lung cells, including microvascular endothelial cells , fibroblasts, human nasal epithelial, and human airway epithelial cells all produced infectious virus after exposure to SADS-CoV.

SADS-CoV is an alphacoronavirus, and is distantly related to human common cold coronaviruses HCoV-229E and HCoV-NL63. However, human sera to HCoV-NL63 did not block infection with SADS-CoV. The good news is that remdesivir, an antiviral drug that inhibits RNA synthesis, blocked replication of SADS-CoV.

Many cell receptors for CoV are known, including ACE2 for SARS-CoV and SARS-CoV2, DPP for MERS-CoV, and APN for HCoV-229E. Antibodies against these cell proteins do not block infection of cells with SADS-CoV, indicating that a different cell receptor is bound to initiate infection with this virus.

These observations indicate that SADS-CoV can infect primary cells from the human respiratory tract. Consequently, this virus should be considered a pandemic threat. What should be done to prevent another devastating pandemic such as the one caused by SARS-CoV-2? Without doubt, antiviral drugs that inhibit SADS-CoV (and a wide range of bat SARS-like CoV) should be identified. Remdesivir is a start but it can only be given intravenously, limiting its utility. Furthermore, humans who work in swine herds should be routinely screened for the presence of SADS-CoV-like viruses.

In the wake of the SARS-CoV-2 pandemic, we can no longer ignore the threats to humanity posed by CoV and other viruses that circulate in bats, rodents, and other non-human animals. We could have prevented the SARS-CoV-2 pandemic with the scientific knowledge obtained before 2019. Have we learned a lesson for the next pandemic?

Filed Under: Basic virology, Information Tagged With: coronavirus, COVID-19, pigs, remdesivir, SADS-CoV, SARS-CoV-2, severe acute diarrhea coronavirus, spillover, swine, viral, virology, virus, viruses, zoonosis

TWiV 582: This little virus went to market

12 January 2020 by Vincent Racaniello

TWiV provides updates on the new coronavirus causing respiratory disease in China, the current influenza season, and the epidemic of African swine fever, including determination of the three-dimensional structure of the virus particle.

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Show notes at microbe.tv/twiv

Filed Under: This Week in Virology Tagged With: african swine fever virus, capsid, China, coronavirus, cryo-electron micrography, giant virus, Huanan Fish Market, influenza, influenza excess mortality, influenza like illness, influenza vaccine, pig, swine, three dimensional virus structure, viral, virology, virus, viruses, Wuhan pneumonia, zoonosis

TWiV 445: A nido virology meeting

13 June 2017 by Vincent Racaniello

From Nido2017 in Kansas City, Vincent  meets up with three virologists to talk about their careers and their work on nidoviruses.

Show notes at microbe.tv/twiv

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Filed Under: This Week in Virology Tagged With: african swine fever virus, coronavirus, cow, flavivirus, Nido2017, nidovirus, susceptibility, swine, vaccine, viral, virology, virus, viruses

Transgenic pigs resistant to foot-and-mouth disease

23 July 2015 by Vincent Racaniello

FMD_note
Image credit

Foot-and-mouth disease virus (FMDV) infects cloven-hoofed animals such as cattle, pigs, sheep, goats, and many wild species. The disease caused by this virus is a substantial problem for farmers because infected animals cannot be sold. Transgenic pigs have now been produced which express a short interfering RNA (siRNA) and consequently have reduced susceptibility to infection with FMDV.

FMDV is classified in the picornavirus family which also contains poliovirus and rhinoviruses. The virus is highly contagious and readily spreads long distances via wind currents, and among animals by aerosols and contact with farm equipment. Infection causes a high fever and blisters in the mouth and on the feet – hence the name of the disease. When outbreaks occur, they are economically devastating. The 2001 FMDV outbreak in the United Kingdom was stopped by mass slaughter of all animals surrounding the affected areas – an estimated 6,131,440 – in less than a year.

Vaccines against the virus can be protective but they are not an optimal solution. One problem is that antigenic variation of the virus may thwart protection. In addition, countries free of FMDV generally do not vaccinate because this practice would make the animals seropositive and prevent their export (it is not possible to differentiate between antibodies produced by natural infection versus immunization). Furthermore, if there were an outbreak of foot-and-mouth disease in such countries, the rapid replication and spread of the virus would make vaccination ineffective – hence culling of animals as described above is required. Clearly other means of protecting animals against FMDV are needed.

Synthetic short interfering RNAs (siRNA) have been shown to block viral replication in cell culture and in animals. To achieve such inhibition, short synthetic RNAs complementary to viral sequences are produced in cells. Upon infection, these siRNAs combine with the cellular RNA-induced silencing complex (RISC) which then targets the viral RNA for degradation.

To determine if siRNA could be used to protect pigs from foot-and-mouth disease, a complementary viral sequence was first identified that blocks FMDV replication in cell culture by ~97%. A vector containing this siRNA sequence was then used to produce transgenic pigs. Such animals not only express the antiviral siRNA, but as the encoding vector is present in germ cells, it is passed on to progeny pigs.

Expression of the siRNA was confirmed in a variety of transgenic pig tissues, including heart, lung, spleen, liver, kidney, and muscle. In fibroblasts produced from transgenic pigs, virus replication was reduced 30 fold. When transgenic pigs were inoculated intramuscularly with FMDV, none of the animals developed signs of disease such as fever or blisters of the feet and nose. In contrast, control non-transgenic pigs developed high fever and lesions. Viral RNA levels in the blood of transgenic pigs were 100-fold lower than in control animals. At 10 days post-infection no viral RNA was detected in heart, lung, spleen, liver, kidney, and muscle, while high levels were observed in these organs from non-transgenic controls.

These results show that siRNAs can protect transgenic pigs from FMDV induced disease. An important question that must be answered is whether transgenic pigs still contain enough virus to transmit infection to other animals. In addition, siRNAs are short – 21 nucleotides – and a mutation in the viral genome can block their inhibitory activity. Therefore it would be important to determine if mutations arise in the FMDV genome that lead to resistance to siRNAs.

Even if transgenic siRNA pigs do not transmit infection, and viral resistance does not arise, I am not sure that consumers are ready to accept such genetically modified animals.

Filed Under: Basic virology, Information Tagged With: aphthovirus, cattle, cow, cullling, FMDV, foot-and-mouth disease, picornavirus, pig, RNA interference, siRNA, swine, vaccine, viral, virology, virus

TWiV 89: Where do viruses vacation?

4 July 2010 by Vincent Racaniello

Hosts: Vincent Racaniello and Alan Dove

On episode #89 of the podcast This Week in Virology, Vincent and Alan review recent findings on the association of the retrovirus XMRV with ME/CFS, reassortment of 2009 pandemic H1N1 influenza virus in swine, and where influenza viruses travel in the off-season.

[powerpress url=”http://traffic.libsyn.com/twiv/TWiV089.mp3″]

Click the arrow above to play, or right-click to download TWiV #89 (56 MB .mp3, 78 minutes)

Subscribe to TWiV (free) in iTunes , at the Zune Marketplace, by the RSS feed, or by email, or listen on your mobile device with Stitcher Radio.

Links for this episode:

  • Conflicting XMRV papers on hold
  • Leak of PNAS paper
  • CDC study on XMRV in CFS patients (Retrovirology) and Science update
  • Where influenza viruses travel in the off season (EurekaAlert! and PLoS Pathogens)
  • NPR article on Ebola siRNA treatment (thanks, Andreas!)
  • Priming mechanism for reovirus entry (thanks, Agyeman-Badu!)
  • Wired article on science PR (thanks, Dan!)
  • Letters read on TWiV 89

Weekly Science Picks

Alan – Tree of Life graphic
Vincent
– TEDx Oil Spill

Send your virology questions and comments (email or mp3 file) to twiv@microbe.tv or leave voicemail at Skype: twivpodcast. You can also post articles that you would like us to discuss at microbeworld.org and tag them with twiv.

Filed Under: This Week in Virology Tagged With: CFS, chronic fatigue syndrome, Ebola, ebolavirus, entry, H1N1, influenza, mecfs, pandemic, reassortment, reovirus, retrovirus, seasonal influenza, siRNA, swine, swine flu, viral, virology, virus, xmrv

TWiV #30: A/Mexico/4108/2009 (H1N1)

3 May 2009 by Vincent Racaniello

twiv_aa_2001On episode #30 of the podcast “This Week in Virology”, Vincent, Dick, Alan, and Hamish Young focus on the new H1N1 influenza virus, which originated in swine and is likely to be the next pandemic strain.

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Click the arrow above to play, or right-click to download TWiV #30 or subscribe in iTunes or by email.

Filed Under: Events, Information Tagged With: H1N1, influenza, pandemic, swine, swine flu, TWiV, viral, virology, virus

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