Evolution of genomes, host shifts and the geographic spread of SARS‐CoV and related coronaviruses

Abstract

Severe acute respiratory syndrome (SARS) is a novel human illness caused by a previously unrecognized coronavirus (CoV) termed SARS-CoV. There are conflicting reports on the animal reservoir of SARS-CoV. Many of the groups that argue carnivores are the original reservoir of SARS-CoV use a phylogeny to support their argument. However, the phylogenies in these studies often lack outgroup and rooting criteria necessary to determine the origins of SARS-CoV. Recently, SARS-CoV has been isolated from various species of Chiroptera from China (e.g., Rhinolophus sinicus) thus leading to reconsideration of the original reservoir of SARS-CoV. We evaluated the hypothesis that SARS-CoV isolated from Chiroptera are the original zoonotic source for SARS-CoV by sampling SARS-CoV and non-SARS-CoV from diverse hosts including Chiroptera, as well as carnivores, artiodactyls, rodents, birds and humans. Regardless of alignment parameters, optimality criteria, or isolate sampling, the resulting phylogenies clearly show that the SARS-CoV was transmitted to small carnivores well after the epidemic of SARS in humans that began in late 2002. The SARS-CoV isolates from small carnivores in Shenzhen markets form a terminal clade that emerged recently from within the radiation of human SARS-CoV. There is evidence of subsequent exchange of SARS-CoV between humans and carnivores. In addition SARS-CoV was transmitted independently from humans to farmed pigs (Sus scrofa). The position of SARS-CoV isolates from Chiroptera are basal to the SARS-CoV clade isolated from humans and carnivores. Although sequence data indicate that Chiroptera are a good candidate for the original reservoir of SARS-CoV, the structural biology of the spike protein of SARS-CoV isolated from Chiroptera suggests that these viruses are not able to interact with the human variant of the receptor of SARS-CoV, angiotensin-converting enzyme 2 (ACE2). In SARS-CoV we study, both visually and statistically, labile genomic fragments and, putative key mutations of the spike protein that may be associated with host shifts. We display host shifts and candidate mutations on trees projected in virtual globes depicting the spread of SARS-CoV. These results suggest that more sampling of coronaviruses from diverse hosts, especially Chiroptera, carnivores and primates, will be required to understand the genomic and biochemical evolution of coronaviruses, including SARS-CoV.

Analysis and visualization of H7 influenza using genomic, evolutionary and geographic information in a modular web service

“…In previous reports, we focused on hypothesis‐driven investigation and the development of the web application Supramap (http://supramap.org). We have used Supramap in several studies to perform combined genetic and phenotypic analysis with geographic visualization to understand the spread of viral lineages, key mutations, and host shifts (Janies et al., 2007, 2008, 2010a). Supramap is distinct from tree visualization systems because we use POY (Varón et al., 2010), which can search for alignments and/or trees, diagnose trees, and output data on mutations and/or phenotypic changes.…”

The Supramap project: linking pathogen genomes with geography to fight emergent infectious diseases

“…Thus, Supramap enables character evolution studies in biogeographic and temporal contexts. Below, we include a case study for character evolution in hypothesis driven research on the spread of key mutations in lineages of infectious diseases (Janies et al., 2007, 2008; Hill et al., 2009).…”

“…Only through serological, microscopic and nucleotide sequence characterization was it understood that SARS was caused by a previously undiscovered coronavirus (CoV) (Ksiazek et al., 2003). Furthermore, it was not until the full genome of SARS‐CoV was sequenced, shared and compared via phylogenetics to related coronaviruses from a variety of animals that the zoonotic origins of SARS‐CoV could be put in the evolutionary and geographic context necessary for disease surveillance (Guan et al., 2003; Marra et al., 2003; Rota et al., 2003; Janies et al., 2008).…”

“…In this report, we focus on the implementation and use of Supramap to track the evolution of phenotypes and mutations in sequence data derived from H5N1 influenza over time, hosts, and geography. Supramap has been used to visualize the spread of pathogens carrying key mutations that confer the ability of the pathogen to replicate in novel host species or to resist drugs (Janies et al., 2007, 2008; Hill et al., 2009). Studies in natural history and anthropology are also underway with Supramap.…”

Literature-related discovery: Potential treatments and preventatives for SARS

“…As far as is known, this outbreak was not due to the deliberate release of the SARS-CoV, but rather was a naturally occurring event. The appearance of SARS seems to have involved: 1) a zoonotic origin for SARS-CoV (e.g., horseshoe bats and/or Chiroptera as one wildlife reservoir [7]); 2) transmission to intermediate hosts (e.g., civet cats, raccoon dogs [8]); 3) human contact with these intermediate hosts in Southern China [Guangdong Province, Fall 2002] and subsequent cross-species transmission of the coronavirus to humans [8]; 4) transmission of the virus through both non-hospital personal contact and hospital staff contact [9]; and, 5) global transmission of the virus via travelers from affected regions in Asia to other countries. SARS was eventually controlled through increased hygienic measures (e.g., face mask protection, frequent hand washing, living quarter disinfection), travel restrictions, and quarantine.…”