A Strategy To Estimate Unknown Viral Diversity in Mammals

Anthony, Simon J.; Epstein, Jonathan H.; Murray, Kris A.; Navarrete-Macias, Isamara; Zambrana-Torrelio, Carlos M.; Solovyov, Alexander; Ojeda-Flores, Rafael; Arrigo, Nicole C.; Islam, Ariful; Ali Khan, Shahneaz; Hosseini, Parviez; Bogich, Tiffany L.; Olival, Kevin J.; Sanchez-Leon, Maria D.; Karesh, William B.; Goldstein, Tracey; Luby, Stephen P.; Morse, Stephen S.; Mazet, Jonna A. K.; Daszak, Peter; Lipkin, W. Ian

Estimates of unknown viral diversity (richness) in all mammals and the cost of discovery. Mammals are the reservoir hosts of the majority of emerging zoonoses (2, 3, 18) . If we assume that all 5,486 described mammalian species (19) harbor an average of 58 viruses in the nine families of interest (as estimated here in P. giganteus) and that these viruses exhibit 100% host specificity, the total richness of mammalian viruses awaiting discovery ex-ceeds~320,000. We used the data on expenditures for surveillance and pathogen discovery in this study to calculate the direct cost of discovering all 58 viruses in P. giganteus (see the supplemental material for details of this cost analysis). We estimate this cost to be $1.2 million, including collection and laboratory testing of 7,079 samples. Assuming expenditures to be equal for all host species, the cost of sampling and viral discovery for all mammalian viruses would be approximately $6.3 billion. Accounting for diminishing returns means that discovering 85% of the estimated diversity would be disproportionately cheaper at approximately $1.4 billion. Our estimates of virodiversity and cost of discovery are preliminary; however, we include them to demonstrate (i) how a systematic estimation of total viral diversity could be used to inform better surveillance through strategic resource allocation and (ii) that, given our cost estimates, the discovery of the majority of potential zoonotic viruses is not an unattainable goal over the next few decades. The generation of sequence data will not, of course, in itself prevent pandemics. However, it does provide data that refine our knowledge of the functional relationship between host and viral diversity, including traits associated with increased risk of spillover and subsequent emergence (e.g., viruses closely related to and sharing receptor binding domains with known lethal agents [20] ) and, also, facilitates the development of rapid diagnostic tests for intervention and control. Several important limitations must be considered in our extrapolations, including (i) the assumption that a mean of 58 viruses per species is a reasonable estimate and that host populations are panmictic with respect to viral transmission (such that expanded geographic sampling would not influence viral detec-tions), (ii) the assumption that viruses are not shared by more than one host species, (iii) that only those viruses within the nine families are considered in this estimation, (iv) that the results are limited by the sensitivity and specificity of our tests, and (v) that a similar mean cost of sample collection is incurred across all species. Clearly, many of these limitations and assumptions require additional exploration. For example, while including more viral families in our survey would increase the viral richness estimate, accounting for species turnover (viral sharing between species) would reduce it. Also, while the cost of sample collection in Bangladesh is relatively low because of logistical simplicities, in some regions (e.g., tropical montane forests of Africa and Southeast Asia), the cost of transportation is much higher. Better estimates of the total number of viruses in mammals (and the cost of their discovery) will be achieved iteratively as other hosts are more extensively sampled and tested, additional viral families are included, and the limits of viral detection increase.