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Invaders and infections

München, 07/29/2016

Our globalized transport networks make it possible for hitherto unknown viruses to travel the world. LMU virologist Gerd Sutter has developed a platform for the production of vaccines against these emerging threats.

MERS turns up in South Korea: An outbreak of MERS in Seoul in June 2015 severely disrupted public life. Source: Lee Jin-man/Picture Alliance/AP Photo

The first novel virus to go global got its big chance on February 21st 2003. On that day, the man experts would later call “the super spreader” checked into a Hong Kong hotel on that day. He wasn’t feeling well, was feverish and had a cough. So the next morning the occupant of Room 911, himself a doctor, went to the nearest hospital. He didn’t get around much in the city, but he managed to infect 16 people with a viral pathogen that had been circulating for months in Guangdong Province on the Chinese mainland, less than 200 km away. Based on the diffuse symptoms associated with it, the illness was later dubbed ‘SARS’ an acronym for “Severe Acute Respiratory Syndrome”. At that point, its cause was still unknown.

Over the following 12 hours, the 16 people infected by the index case would bring the infectious agent from Hong Kong halfway round the world, to Vietnam, Singapore and Canada. In the succeeding weeks, it would reach some 30 countries on six continents. Nearly 8500 people were infected, of whom more than 900 died. Epidemiologists would later succeed in tracing nearly half of these cases back to the hotel guest in Hong Kong, who himself succumbed to the disease.

“It suddenly became clear to everyone just how fast an infectious agent can be propagated in the modern world,” says Gerd Sutter, Professor of Virology at LMU. The globe is now one enormous network of commercial interactions: Business people are in Hong Kong today, London tomorrow and New York the next day – and vast numbers of tourists are on the go. With some 35 million flights annually, it is no wonder that airports have become a point of focus for epidemiologists.

“The process has accelerated”
Fear of the SARS virus spread even faster than the pathogen. It was rapidly identified as a member of the so-called coronaviruses, but this did little to allay fears of emerging pathogens and further epidemics, as coronaviruses had been regarded as essentially harmless. People hurriedly cancelled planned trips, airlines lost business, and social life in those locations the virus had reached came to a standstill, with pronounced economic consequences. In the German media, use of the term ‘SARS’ became pervasive, even though not a single fatal case of SARS occurred in the country. Ten years later, the media were recalling the time when “death flew around the world”.

But SARS was only the first global epidemic of the new millennium. Less than a year later, bird flu was making headlines, to be followed by swine flu, Middle East Respiratory Syndrome (MERS) and then the unprecedentedly large outbreak of Ebola fever in West Africa. The latest in the sequence is the Zika virus. Discovered nearly 70 years ago in Africa, it recently reached the Americas, and is now endemic in parts of South America. The rate of emergence of new viral threats has increased in recent years – and this is not just an impression from improved surveillance or media hype. “The process has indeed accelerated,” Sutter confirms.

With globalization, the world has effectively shrunk, which promotes not only the dissemination of goods and services, but also that of viruses and infectious illness. But where do the emerging viruses actually come from, and what factors turn a previously unremarkable virus into a killer? As the SARS example shows, viral breakout is both serendipitous and inevitable. Can these inherently unpredictable interactions be effectively prevented? Do we have reliable strategies to guide the development of vaccines against such threats?

These are some of the questions that concern Gerd Sutter. He works at the Institute for Infectious Diseases and Zoonoses, which is part of LMU’s Faculty of Veterinary Medicine. Around two-thirds of human pathogens originated in animals, and are often harmless to their normal hosts. Over millions of years of evolution, virus and animal host have developed a modus vivendi that enables both to survive and reproduce. In a sense, the new challenges have redirected Sutter‘s research interests from veterinary to clinical medicine. He is now primarily involved in the design of vaccines to protect people from zoonotic viruses like SARS, MERS, bird flu or Ebola. And in this capacity, he has made a name for himself worldwide.

Severe birth defects
Only a few months ago, a panel of experts compiled a list of the most urgent threats for the World Health Organization (WHO). They came up with what one could call “The Hateful 8”, a set of lethal viruses that includes the coronaviruses SARS and MERS, and the Ebola virus and its close relative Marburg virus, both of which induce a hemorrhagic fever leading to severe internal bleeding. Similar symptoms characterize the syndromes caused by Crimea-Congo, Lassa and Rift Valley Fever viruses, while the Nipah virus also causes encephalitis.

The current scare concerns the Zika virus, which is strongly suspected to be responsible for severe birth defects in human neonates. In adults, infections usually take a mild course, sometimes accompanied by a skin rash, headaches and joint or muscular pain. But pregnant women, who may not even realize they are infected, can transmit the virus to the fetus. The health authorities in Brazil have linked the virus to a recent increase in the incidence of microcephaly, a congenital condition characterized by severe perturbation of brain development and malformation of the skull, in newborns. This link is supported by experiments in laboratory models which have shown that the virus infects neuronal precursor cells, which give rise to the nerve cells that populate the cerebral cortex

The rapid spread of the Zika virus in Central and South America prompted the WHO to declare it a “public health emergency of international concern”, in February 2016. Meanwhile, Brazil has initiated a campaign to inform the public of the risk, and mobilized thousands of soldiers who are using insecticides to reduce the numbers of Aedes aegypti, the mosquito that transmits the virus. According to a bulletin from the Robert Koch Institute (RKI) in Berlin, the agency tasked with monitoring the incidence of infectious diseases in Germany, the virus may have reached South America during “an international sporting event” (i.e. the World Cup) “in 2014,” a suggestion that Sutter refers to as “an interesting speculation.”

Page 2: A cozy ecological niche