virology blog

About viruses and viral disease

pigs

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

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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?

Circovirus in Shanghai

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Circovirus genomeRecently thousands of dead and decaying pigs were pulled from rivers in Shanghai and Jiaxing, China. Apparently farmers dumped the animals into the water after the pigs became ill. Porcine circovirus has been detected in the in pig carcasses and in the water.

Porcine circoviruses are small, icosahedral viruses that were discovered in 1974 as contaminants of a porcine kidney cell line. They were later called circoviruses when their genome was found to be a circular, single-stranded DNA molecule. Upon entry into cells, the viral ssDNA genome enters the nucleus where it is made double-stranded by host enzymes. It is then transcribed by host RNA polymerase II to form mRNAs that are translated into viral proteins. There is some evidence that circoviruses might have evolved from a plant virus that switched hosts and then recombined with a picorna-like virus.

Porcine circoviruses are classified in the Circoviridae family, which contains two genera, Circovirus and Gyrovirus. There are two porcine circoviruses, PCV-1 and PCV-2; only the latter causes disease in pigs. Infection probably occurs via oral and respiratory routes, and leads to various diseases including postweaning multisystemic wasting syndrome, and porcine dermatitis and nephropathy syndrome. Virions are shed in respiratory and oral secretions, urine, and feces of infected pigs. Other circoviruses may cause diseases of birds, including psittacine beak and feather disease, and chicken infectious anemia, the latter caused by the sole member of the Gyrovirus genus. There are also circoviruses that infect canaries, ducks, finches, geese, gulls, pigeons, starlings, and swans.

We have no good evidence that porcine or avian circoviruses can infect humans. In the United States, porcine circovirus sequences can be detected in human feces. These most likely originate from consumption of pork products, most of which also contain porcine circoviruses. Circovirus sequences have also been found in commonly eaten animals such as cows, goats, sheep, camels, and chickens. Outside of the United States, the circoviruses found in human stools do not appear to be derived by meat consumption and might cause enteric infections.

Recently both PCV-1 and PCV-2 sequences were detected in Rotarix and RotaTeq, vaccines for the prevention of rotavirus disease in infants. The source of the contaminant was trypsin, an enzyme purified from porcine pancreas, which is used in the production of cell cultures used for vaccine production. Use of these vaccines was temporarily suspended, but resumed when the Food and Drug Administration concluded that there is no evidence that porcine circoviruses pose a safety risk to humans.

The good news is that porcine circoviruses in Shanghai’s waters are no danger to humans. But it is not a good idea to have rotting pig carcasses in a river that supplies some of Shanghai’s drinking water.