Virus update: Pigs as mixing vessels

So far, the last year has seen the introduction of at least two new viruses that directly or indirectly affected the pig and pork industry. Of them, the novel (H1N1) 2009 influenza A virus has attracted the most attention as temporal trade bans and worldwide worries were amongst the consequences. Recent research has shed some light on the diseases’ origins and dangers.

By Vincent ter Beek

Since the first signs of pandemic (H1N1) 2009 in humans, at the end of April, the pig industry has been looking anxiously at the consequences of this outbreak on national and international pig trade and consumption. A consistent emphasis by many media to call the novel influenza A ‘swine flu’ most certainly has not helped the image of pork being safe to eat – irrespective of the question whether there is some relationship between swine origin and the H1N1 pandemic in humans.

It is hard to establish as to what the novel virus’ exact origins could be. It has been possible for scientists however, to dissect the virus and find out what it is made of. The virus is a so-called ‘multiple reassortant’. The novel virus is most probably a mixture of a swine triple reassortant virus found in North American and Asian pigs plus Eurasian swine influenza viruses (H1N1). The new virus thus combines avian-like gene segments, human-like gene segments and swine-like gene segments.

Interestingly, for humans, the virus is atypical in the sense that it oddly affects younger to middle-aged people and that it struck in the summer season in the northern hemisphere, instead of winter. Using this knowledge, several academic research institutes have already been trying to establish whether the novel outbreak does have any relationship to pigs at all. Their outcome: there does seem to be some kind of relationship between the virus and pigs. The US Agricultural Research Service (ARS) focused on the question whether pigs can catch the pandemic (H1N1) 2009 virus – and they reached a positive answer. The virus was only detected in the respiratory tract of infected pigs and the virus did not appear to spread and replicate in other tissues, based on the day 5 post infection samples.

In the field

The situation in the field reflected these outcomes as at the time of publishing; several cases in Canada have been reported to be infected, two in Argentina, three in Australia, one in Singapore, three in Northern Ireland, one in the Republic of Ireland and one in Norway.

Initially, these pigs were thought to be infected by humans, but this pattern of outbreaks at pig farms throughout the world could point in a different direction, says Prof Ian Brown, Veterinary Laboratories Agency, Weybridge, UK. “Whether the virus only came from people is quite questionable,” he says. “The evidence for a direct link between an infected human that then passes the virus to pigs has only been shown by laboratory testing in two cases so it’s important that the pig industry understands this. In my opinion, the virus will continue to spread among pigs – and these current infections may mark the beginning of a widespread expansion in the coming months. My judgment is that these cases may only reflect a fairly small number of the total farms affected.”

The virus has not only proven to be prevalent in pigs – but also causing disease. So far, the disease caused by the virus amongst pigs seems to be rather mild, as was shown by preliminary trials at his own VLA and at Kansas State University, USA. Brown is quick to put his preliminary results into perspective.

“You have to keep in mind that our study was done with naïve, antibody-free pigs, so they had no other previous immunity. They were fully susceptible, and that may explain the results. In the field, the situation may be more complex, as pigs that may have been in contact with Swine Influenza Virus (SIV) previously could be less obviously affected, but the virus may still be able to transmit amongst pigs in close contact. The prior immunity to influenza may mask the disease or reduce the ease with which the virus can transmit.”

Although the VLA did not carry out any tests on older pigs, i.e. fatteners or breeding sows, Brown judges that the disease will only cause ‘mild severity’ in pigs – although dynamics might be different in several types of animals. “In our test, we infected pigs of four to five weeks of age and what we saw was a range of individual susceptibilities. We directly infected eleven pigs. Some developed quite severe disease, others only developed signs like sneezes or an increased naval discharge, which may hardly be noticeable in the field. What we did notice was a reduction in weight gain,” Brown says. “In combination with other factors including secondary bacterial infections, however, it may progress into something more severe or chronic.”

Existing SIV vaccines do not seem to have any effect on pigs, as was shown in research by the ARS. Three viruses, isolated from persons in California, New York and Mexico were grown in vitro and tested on pigs, vaccinated to ‘conventional’ swine influenza virus.

Transmission

The VLA study also showed that infected animals were able to transmit the virus to naïve contact pigs successively for at least four cycles of transmission, suggesting the virus could become established in susceptible pig populations if introduced. This characteristic in pigs may be interesting since pigs are known to be so-called ‘mixing vessels’ – or animals that allow reassortment of viruses to happen. According to Brown, this ‘unfortunate label’ is related to a rather unique quality of pigs: “They are equally susceptible for strains from human and avian origin. In most other host species, you’ll see that it is either one or the other.

Pigs’ cell receptors respond the same to viruses from avian and mammalian origin – so in pigs, there is an equal threshold and this makes it the ideal ‘mixing vessel’.” Reassortment, for that reason, will happen, Brown believes – potentially in SE Asia, but also elsewhere where there are large numbers of pigs andvirtually all the world’s viruses present. But he doesn’t expect this as a new potential virus to be a threat to public health – and he uses history to prove that thesis. “Never say never, but I think nothing severe will happen.

This we could see from previous pandemics, like in 1968, when the H3N2 reassorted with other viruses in pigs. These new viruses, however, did not spread amongst people. They affected the occasional person but had a very limited impact. So: further reassortment is likely to happen; but there is no strong evidence to support these viruses posing a greater threat to humans.”

One more ‘new’ pig virus: Ebola-Reston
At the end of December 2008, traces of the Ebola-Reston virus were found in pigs on two sites in the Philippines, in Pangasinan province and Bulacan province, see Figure 1. A recent study, published in Sciencemagazine, by Roger W. Barrette and others, clarified what exactly had been going on at the time – and what could be the significance of the finding. The Ebola virus is a member of the Filoviruses family. Scientists discern between five different species of Ebola, of which Ebola-Reston Virus (REBOV) is the only one not associated with disease in humans – so far, only with disease in non-human primates, in a couple of macaques. The finding of the virus in (sick) pigs was a new development for that reason. Samples sent to the Special Pathogens Branch at the Centers for Disease Control (CDC) in Atlanta, Georgia, USA, confirmed that REBOV was found in pigs that had also tested positive for Porcine Respiratory and Reproductive Syndrome Virus (PRRSV).

The article in Science went on to say that: “The isolation of REBOV from swine represents an extension in the known host tropism. Given the broader genetic diversity and geographic distribution of REBOV in swine, it is possible that REBOV spilled over to monkeys and swine from an as yet unidentified host.” Bats were suggested as a reservoir, the article said. It continued saying that ‘the role of swine as either an incidental host or an integral part of the virus’ transmission cycle has yet to be determined. “Because evidence of coinfection with PRRSV, an arterivirus, was found with REBOV, we can speculate about a link between coinfection and disease in swine.” The article’s conclusion says: “There is concern that its passage through swine may allow REBOV to diverge and shift its potential for pathogenicity. It is expected that future epidemiology and pathogenesis studies will shed light on the potential reservoirs, mode(s) of transmission, mechanisms of pathogenesis, prevalence of REBOV in nature, and its consequences of agricultural industries and trade.”

Influenza viruses – a quick overview
Three main influenza types are known (A, B and C), of which A is the most prevalent. In humans and animal species, innumerable influenza A varieties exist (see Table 1). An influenza A virus consists of eight genes, which each can be divided in several types as well. This endless pool of characteristics allows a potential rapid modification of the influenza virus. Influenza type A is generally classified by the proteins hemagluttinin (H, 16 varieties) and neuraminidase (N, 9 varieties), both present on the virus’ surface. This leads to 144 different subtypes. Classical Swine Influenza (SIV) is usually an H1N1 variety as well.

Source: Pig Progress Volume 25 nr 8