Читать книгу Viruses: More Friends Than Foes (Revised Edition) - Karin Moelling - Страница 18

CoV-2 most probably originates from bats and is a zoonotic disease, meaning that it started in animals before it reached humans. An intermediate was perhaps the pangolin, a scaly ant-eating mammal, sold on the wet market in Wuhan; intermediate hosts are frequently involved. In a paper in the New England Journal of Medicine, G. Gao pointed out that the first infected patients had no link to the market. Perhaps an amplification occurred there or an indirect transmission through latently infected people. The bats are a special kind, the horseshoe bat, which exists in Yunnan (1600 km away), and bats were hibernating at that time.

Bats are the source of many viruses. They have a special immune system: the antiviral interferon system activates another factor, which means almost a doubling of immunity and of protection against viruses. Therefore, bats are often carriers and transmitters of viruses without getting ill themselves. There are about 1500 caves in China where millions of bats live. They rarely infect humans directly, but known viruses, such as Ebola or Marburg disease, and the new coronaviruses originate from bats. Also the SARS outbreak in 2003 was traced back to bats and an intermediate host, the civet cat, which raised the question whether this could happen again.

In 2015, Wuhan’s WIV obtained a high-containment laboratory at the highest biosafety level 4 (BSL-4). This was the first laboratory of this type in mainland China. The construction was already approved in 2003 as a consequence of the SARS outbreak in that year. After this SARS outbreak, intensive research started to understand it and prevent a repeat. The laboratory was designed and constructed with French assistance with the BSL-4 Institute in Lyon as model. A co-operative agreement was made on prevention and control of emerging infectious diseases in 2004. It took until 2014 to finish the construction. Viruses studies there included the Ebola, Lassa, Hendra and Nipah viruses, while SARS does not require BSL-4.

The goal was to study how viruses mutate into new strains and cause diseases, and to develop treatments based on antibodies and small molecules.

A special question was how zoonotic viruses, such as SARS and Ebola, spread among humans. In biosafety laboratories the air is filtered through HEPA filters; the rooms are under low pressure so that viruses will stay inside and do not escape by air flow; researchers have full-body protective suits with their own air supply for breathing; and masks are used. Biosafety labs contain clean benches with hoods, equipped with filters and vertical air flow which acts like an “air curtain” and separate the researcher from his/her work.

In a laboratory at the University of North Carolina in the USA, researchers tried in 2015 to analyze bat viruses, and generated recombinant viruses which could bind to human lung cells. The authors state that such viruses need to be constructed so that one can learn about pandemic viruses. However, the virus became frightening, and the authors mention in their paper that such viral chimeras will no longer be produced. The procedure is called “gain of function” (GOF) for viruses gaining new characteristics. The danger of an epidemic was considered high, and continuation of the experiments was forbidden (Nature Medicine 21, 1508, 2015). The authors are from the USA, China and Switzerland. The main contribution came from the USA, including finances, as stated in a later commentary on the paper. A recent footnote from 2020 states that this synthetic virus could not have contributed to the present pandemic.

I was surprised that SARS-coronaviruses do not require work in BSL-4 but only BSL-3 laboratories. Perhaps the BSL-4 laboratory was used, in spite of this, when it became available. On March 17, 2020 an article in Nature Medicine stated “that the authors do not believe that any type of laboratory-based scenario is plausible” (Nature Medicine 26, 450, 2020). The CoV-2 has an unusual polybasic sequence within the spike protein not found in other coronaviruses. Where did it originate? This basic stretch is a cleavage site for furin proteases, also detected in Influenza where it increases its pathogenicity. Recently a similar sequence was detected in a natural bat virus isolate.