Editor's note: Science Scan is a roundup of recently published biotechnology-relevant research.
A blue-ribbon consortium of six World Health Organization (WHO) medical centers confirmed that a novel coronavirus is the primary cause of SARS - severe acute respiratory syndrome. This emergent disease was first reported in the People's Republic of China in November 2002. From there, SARS spread to other Asian countries, then to North America and Europe. By July 3, the outbreak had resulted globally in 8,439 reported cases, of which 812 were fatal.
An article in The Lancet, dated July 22, 2003, reports the WHO finding under the title "Newly discovered coronaviruses as the primary cause of severe acute respiratory syndrome." The principal co-authors are virologists, pathologists and immunologists at Erasmus University in Rotterdam, the Netherlands.
Many, if not most, viruses owe their names to the geographic location in which they are first discovered. Coronaviruses are in a league of their own. Their virions resemble the petal-shaped projections visible during the total eclipses around the rim of the hidden sun - called the solar corona.
The six virology centers in the WHO consortium were from Hong Kong, Singapore, Germany, the UK, Vietnam and France.
The co-authors did clinical and experimental studies to assess the role of this newly discovered coronavirus in SARS. Their paper began: "We tested clinical and postmortem samples from 436 SARS patients in six countries for infection with SARS-CoV [coronavirus], human metapneumovirus and other respiratory pathogens." (Pneumovirus causes severe lower respiratory tract disease, often in infants.)
The Rotterdam researchers infected four cynomolgus macaques with pneumonia similar to that in human beings with SARS, combined with SARS-CoV in an attempt to replicate human SARS. They did necropsies on day six after that challenge inoculation. The four primates excreted SARS-CoV from nose, mouth and pharynx from two days after infection. Three of the four developed diffuse alveolar damage from a postmortem lung sample, similar to that in human SARS patients. The infection was diagnosed in 329 (75 percent) of 436 human SARS patients, as well as 41 (12 percent) of 335 diagnosed with pneumovirus. "Until now," the co-authors noted, "immunohisto-chemical detection of SARS-associated coronavirus [SARS-CoV] in SARS-associated lesions has not succeeded."
The Lancet paper concluded that "replication in SARS-CoV-infected macaques of pneumonia similar to that in human beings with SARS, combined with the high prevalence of SARS-CoV infection in SARS patients, fulfills the criteria required to prove that SARS-CoV is the primary cause of SARS." Those criteria rely largely on the classic Koch's postulates, which posit six criteria that need to be fulfilled for a particular microorganism to be proved the causal agent of a disease. Laboratory investigations of clinical and postmortem samples, as already presented, fulfilled the first three criteria: (1) isolation of the virus from diseased hosts, (2) cultivation in diseased host cells, and (3) proof of filterability (to exclude larger pathogens).
Results of studies on the four macaque monkeys, the paper pointed out, fulfill the remaining three postulates: (4) production of a comparable disease in the original host or (5) a related species, and (6) re-isolation of the virus. The Lancet article concluded on a cautionary note: "SARS-CoV infection primarily affects epithelium of the lower respiratory tract, with potentially severe consequences for respiratory function."
A Protein Called WAVE2, And Its Gene, WAVE2, Control Cardiovascular Health, Cell Migration
WAVE2 is a key protein that helps the cardiovascular system develop normally. During development, it is essential for the normal formation of cardiac blood vessels. Biochemists at the University of Tokyo reported research on WAVE2 in Nature, dated July 24, 2003. Their paper is titled "WAVE2 is required for directed cell migration and cardiovascular development."
The co-authors produced knockout mice lacking the WAVE2 gene. The embryos died from hemorrhages at 10 days. Analysis revealed that the cells lining blood vessels had branched and sprouted less than normal endothelial cells. WAVE2 is known to be involved in cell migration, a phenomenon essential for a variety of fundamental biological processes, including immune cell migration, cancer metastasis and formation of body organs. The KO mice were unable to form lamellipodia - small, protrusive membrane structures that help a cell to move. The authors suggest that lack of the functional WAVE2 protein impairs angiogenesis in live animals.