Infectious Diseases

Viruses need entry proteins to penetrate the cells where they will replicate. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) version is called the spike or S protein.

The S protein, also the target of the current vaccines, is quickly adapting to its new human hosts. It took its first major step in this direction early in 2020, when its amino acid 614 (of 1297) changed from an aspartic acid (D) to a glycine (G). Viruses bearing this D614G mutation transmit among humans more rapidly and now form the majority in circulation.

On page 525 of this issue, Zhang et al. (1) use careful structural analyses to reveal how D614G changed the S protein to accelerate the pandemic.

The work of Zhang et al. also reveals more about the natural history of the virus. The notable emergence of D614G suggests that the acquisition of a destabilizing furin site was a recent event. The virus could easily lose this site, as it does frequently in cell culture systems, implying that it in some way facilitates human transmission.

This is not a conclusion that most students of human coronaviruses would have anticipated, given that SARS-CoV-1, which transmits with reasonable efficiency, lacks this site, whereas the more distantly related MERS coronavirus bears this site and transmits poorly. How the SARS-CoV-2 furin site promotes new human infections remains a key open question in the field.

read the entire article at https://science.sciencemag.org/content/372/6541/466

Simple in structure but advanced in function, viruses exist in a category that lies between the inert and the living.

Slightly ovoid in shape and somewhat blurred at the edges, the black splotches were scattered across a mottled gray background, looking much like a postmodern painting. At a meeting of the Medical Society of Berlin in 1938, Helmut Ruska, a German physician and biologist, was presenting the first images ever seen of virus particles. The splotches were members of the poxvirus family, specifically ectromelia, visualized directly in the lymph fluids of infected mice. 

Thanks to the invention of the electron microscope, then known as the Übermikroscop, scientists could finally observe—actually see—what was already known to exist: the minuscule and mysterious world of viruses. Ruska’s brother, Ernst, a physicist, had built the first prototype of the instrument while completing his Ph.D., but Helmut saw the device’s potential application to the field of biology. Helmut and his colleagues went on to gather nearly 2,000 black-and-white images by the end of 1939. Their collection included a variety of pathogens known to infect humans and plants, including the variola virus (which causes smallpox) and tobacco mosaic virus (the first virus ever discovered).

Just over 80 years later, scientists published the first images of SARS-CoV-2, the novel virus that causes COVID-19. To reveal its iconic spike protein, they used an instrument similar to Ruska’s. The black-and-white images visually confirmed that this was a member of the coronavirus family, enabling scientists around the world to begin drawing upon existing knowledge of such viruses from years of prior research. Scientists were able to directly observe this new virus soon after a cluster of patients in China was diagnosed in late December 2019 with a pneumonia of unknown cause. By March 2020, COVID-19 had been declared a pandemic by the World Health Organization.

Events moved far more slowly in previous pandemics. The Black Death pandemic in the mid 1300s killed more than one-third of Europe’s population in four years, without anyone knowing what caused it. By the time of the 1918 flu pandemic, scientists understood the disease’s cause but couldn’t see the virus or test for it. When SARS-CoV-2 emerged, the value of basic science research conducted many decades earlier became quickly evident in the form of innovative tools for virus detection. Researchers can now sequence novel viruses and study their genomes, but even so the electron microscope continues to offer a unique “open” view of such pathogens.

There may be more viruses than there are stars in the universe.

Basic science research being conducted today will play a critical role in helping us to understand their past, present, and future—and better prepare us for the emergence of still more novel viruses.

read the entire essay at https://nautil.us/issue/99/universality/the-vast-viral-world-what-we-know-and-dont-know