Emerging Viruses: The Evolution of Viruses and Viral Diseases Author(s): Stephen S. Morse and Ann Schluederberg Source: The Journal of Infectious Diseases, Vol. 162, No. 1 (Jul., 1990), pp. 1-7 Published by: Oxford University Press Stable URL: http://www.jstor.org/stable/30127833 Accessed: 18-08-2014 21:02 UTC

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Fromthe NationalInstitute of Allergy and Infectious Diseases, the FogartyInternational Center of the National Institutesof Health, and the RockefellerUniversity

Emerging Viruses: The Evolution of Viruses and Viral Diseases

Stephen S. Morse and Ann Schluederberg From the ,New York,New York,and the National Institute of Allergy and InfectiousDiseases, National Institutesof Health, Bethesda, Maryland

Challengedby the sudden appearanceof AIDS as a major rus and host can follow severalpossible lines, and pathogens public healthcrisis, the National Instituteof Allergy and In- may not always evolve towardslower virulence. In a model fectious Diseases and the FogartyInternational Center of the developed by Levin (describedin [3]), for example, a virus NationalInstitutes of Health(NIH), togetherwith The Rocke- strain that kills much faster will not be favoredover a less- feller University,jointly sponsoredthe conference "Emerg- virulent strainif it has a modest transmissionadvantage, but ing Viruses: The Evolution of Viruses and Viral Diseases" it will prevailif it is much more readily transmittedthan the held 1-3 May 1989 in Washington,DC. It was convened to less-virulentstrain. Examples such as myxomatosisin Aus- consider the mechanismsof viral emergence [1]and possible tralia supportthe notion that in the tradeoffbetween trans- strategiesfor anticipating,detecting, and preventing the emer- missibilityand virulence, many viruses evolve toward a middle gence of new viral diseases in the future. To providea broad course, favoringtransmissibility but allowing them to retain perspective,participants comprised virologists, infectious dis- some virulence. Viruses that are transmissibleover a long ease specialists, theoreticalbiologists, historians, epidemi- time (e.g., human immunodeficiencyvirus [HIV]) have a ologists, ecologists, and molecularbiologists (see below for selective advantageeven when their effective rates of trans- program and participants). mission are relatively low [5]. Although mathematicalapproaches offer useful insights, and Haase caution that models will often inade- Theoretical Considerations May prove quate in predicting outcomes because viral emergence and The enormity of the problem was outlined in the keynote host interactions are complex, being dependent on both address by Lederberg,who said that humankind'sonly real genetics of the host and externalconditions. For example,as competitorsfor dominionof the planetare viruses, which can discussed by Lovejoy, there are many examples of disease serve as both parasites and genetic elements in their hosts. emergenceprecipitated by environmentalchange, but it is im- Not only do theyhave considerable genetic plasticity, enabling possible at presentto predictor model accuratelyhow global them to evolve in new directions,but their genetic and meta- warmingor other possible environmentalchanges will affect bolic entanglementswith cells uniquelyposition them to medi- viral disease emergence. ate subtle, cumulativeevolutionary changes in their hosts as well. Their effectsare not alwaysso subtle, however;viruses Historical Lessons on Disease Emergence also can decimate a population. The fact that naturalselec- tion in the long run favorsmutualism offers only limited en- According to McNeill [6], the most striking examples of couragementto the human race, as too many people might emergenceof infectious diseases arose from new patternsof suffer as the result of viral mutation before an equilibrium human movement, leading to new contacts across what had could be reached. [2] previouslybeen geographicboundaries that containeda dis- Accordingto May and Anderson [3, 4], coevolutionof vi- ease. Examples are the introductionof smallpox into the Americas and of syphilis into Europe. Disease emergence resulting from expanded geographic Received 11 December 1989; revised 18 January 1990. boundariesof viruses or their vectors was a recurringtheme Financial NationalFoundation for Infectious Hoffman-La support: Diseases, discussed in talks by Johnson, Monath, Evans, Shope, and Roche, Lilly ResearchLaboratories, and Merck Sharp8c Dohme Research Laboratories(for the conference);RR-03121 and RR-01180,National Insti- others. Yellow fever probablyemerged in the New Worldas tutes of Health (to S. S. M.). a result of the African slave trade, which broughtAedes ae- and Dr. S. Morse, the Rockefeller Reprints correspondence: Stephen gyptiin watercontainers of ships. Similarly,the rise of dengue University, 1230 YorkAve., Box 2, New York, NY 10021-6399. hemorrhagicfever in SoutheastAsia in the late 1940s is at- The Journalof InfectiousDiseases 1990;162:1-7 tributedto to cities with water ? 1990by The Universityof Chicago.All rightsreserved. rapidmigration open storage, 0022-1899/90/6201-0001501.00 which favoredproliferation of the mosquito or other suitable

This content downloaded from 155.58.212.160 on Mon, 18 Aug 2014 21:02:31 UTC All use subject to JSTOR Terms and Conditions 2orse l chluederberg ID 990;162 July)

Table 1. Some examples of "emerging"viruses. Symptoms Distribution Natural host

Orthomyxoviridae(RNA, 8 segments) Influenza Respiratory Worldwide (from China) Fowl, pig Bunyaviridae(RNA, 3 segments) Hantaan, Seoul, and others Hemorrhagicfever with renal syndrome Asia, Europe, USA Rodent (e.g., Apodemus) Rift Valley fever* Fever, may also cause hemorrhage Mosquito; ungulate M8SJ1(VirusOropouche* Fever Brazil, Trinidad, Panama Midge Togaviridae (Alpha) (RNA) O'nyong-nyong* Arthritis, rash Africa Mosquito Sindbis* Arthritis, rash Africa, Europe, Asia, Australia Mosquito; bird Flaviviridae (RNA) Yellow Fever* Fever, jaundice Africa, South America Mosquito; monkey Dengue* Fever, may also cause hemorrhage Asia, Africa, South America, Mosquito; human; Caribbean monkey Rocio* Encephalitis Brazil Mosquito; bird KyasanurForest* Encephalitis India Tick; rodent Arenaviridae (RNA, 2 segments) Junin (Argentine hemorrhagicfever) Fever, hemorrhage South America Calomys musculinus Machupo (Bolivian hemorrhagicfever) Fever, hemorrhage South America Calomys callosus Lassa fever Fever, hemorrhage West Africa Mastomys natalensis Filoviridae (RNA) Marburg, Ebola Fever, hemorrhage Africa Unknown Retroviridae(RNA + reverse transcriptase) Human immunodeficiency virus AIDS, AIDS-related complex Worldwide ? Primate Poxviridae (DNA) Monkeypox Smallpox-like Africa (rainforest) Squirrel NOTE. Boldface indicates viruses with greatest apparentpotential for emergence in the near future. * Transmittedby arthropodvector.

vectors. Of currentconcern in the USA is the fact thatAedes Otheranimals, especially primates,are importantreservoirs albopictus, an aggressive and competent dengue virus vec- for transferby arthropods. tor, was broughtto Houston in used Asian tires and has es- Accordingto Monath,MOO of the ^20 knownarthropod- tablished itself in at least 17 states. Krause noted that with borne viruses (arboviruses)cause humandisease. At least 20 dengue hemorrhagicfever "lappingat our shores,"we have of these might fulfill the criteria for emerging viruses, ap- a potentially serious public health problem in the making. pearing in epidemic form at generally unpredictableinter- vals. Most arboviruseshave enzootic cycles involvinga vector (e.g., mosquitoes, ticks, or biting flies) and wild vertebrate Recent Examples of Emerging and Potentially hosts, most of which rarelymanifest overt disease. Many ar- Emergent Viruses boviruses can also be transmittedvertically within their vec- Table 1 lists some viruses that have been associated with tors, assuringsurvival over winters or dry seasons. Periodic "emergent"disease. Disease emergenceoften followsecologic amplificationoccurs when vector and susceptiblehost popu- changes caused by human activities, such as agricultureor lation densities and other factors favorrapid virus transmis- agriculturalchange, migration, urbanization,deforestation, sion, and it may be followed by epidemics in humans or or dam building. For example, Argentinehemorrhagic fever domestic animals. In such situations,arboviruses may enter increasedas agriculturalchanges favoredthe rodentthat car- into a second transmissioncycle involving one or more ar- ries this virus. thropodvector species differentfrom the enzootic vector spe- Surprisingly,most emergentviruses are zoonotic, with nat- cies and humansor domestic animals as viremic hosts. This ural animalreservoirs a more frequentsource of new viruses makes surveillancedifficult. Eldridgedescribed how knowl- than is the sudden evolution of a new entity. The most fre- edge of mosquitoevolutionary relationships could help to pre- quent factor in emergence is humanbehavior that increases dict new mosquito vectors. the probabilityof transferof viruses from their endogenous Anothervirus of currentinterest in the USA, Seoul virus, animalhosts to man. Rodentsand arthropodsare most com- was identified MO years ago in Koreaas a Hantaan-likevi- monly involvedin directtransfer, and changesin agricultural rus whose naturalhost is the urbanrat. Serologic surveysde- practices or urbanconditions that promote rodent or vector tect it worldwide, including seroprevalencerates of 1296 in multiplicationfavor increased incidence of human disease. urban rats in Philadelphiaand ~64% in Baltimore rats, as

This content downloaded from 155.58.212.160 on Mon, 18 Aug 2014 21:02:31 UTC All use subject to JSTOR Terms and Conditions JID 1990;162 (July) Emerging Viruses 3 reportedby LeDuc et al. [7]. Although acute hemorrhagic caused a fatalepidemic in chickens in Pennsylvania[16]. The feverwas not identifiedin inner-cityBaltimore, 1.3% of 1148 point mutation in the H gene changed thr to lys, exposing local residentswere antibody-positiveand the possibility of a previously glycosylated site. Similarly, and remarkably,if viral association with chronic renal disease is under study. pigs are infectedexperimentally with an avirulentmutant [17], Intensivesurveillance in Africa duringthe smallpoxeradi- the swine virulent parentalphenotype emerges within a few cationprogram identified a humancase of monkeypoxin Zaire days, indicatingrapid evolution and emergencein vivo of the in 1970. Since then, 404 cases have been reported,virtually virulent form [18]. all among children living in villages in tropical rain forests For viruses with nonsegmentedgenomes, recombination [8]. The virus appears unable to be sustained by naturally provides another genetic avenue for emergent diseases, ac- occurringperson-to-person spread; both monkeys and humans cordingto Strauss.For instance,viral genetic sequence anal- are probably infected incidentally by contact with infected ysis revealedthat western equine encephalomyelitisvirus, an squirrels. Fenner commented that it was difficult to under- alphavirus,arose from a recombinationevent that seems to standwhy monkeypoxvirus spreadso poorly;if it spreadread- have involved a Sindbis-like virus and eastern equine en- ily from person to person by the respiratoryroute it would cephalomyelitisvirus, probablyoccurring 100-200 yearsago constitutea risk similarto thatof smallpox. In fact, however, [19]. Monathsuggested that Rocio encephalitisvirus mayhave conversionof forestto agriculturalland appearsto be reduc- arisen similarly. Genetic recombinationalso seems to have ing its transmissionfrom wildlife and its incidence in coun- occurredbetween the envelopeprotein genes of humanT lym- tries of West Africa. photropic virus (HTLV)-I and HTLV-II[20]. Because little is known about interspecies transferto hu- mans at the molecularlevel, two recent examplesin animals, Mutation Frequency canineparvovirus and seal plague, were presentedby Parrish and Mahy, respectively. Canine parvovirus2 may have de- The mutationrate of any genome is inverselyproportional scended from the feline parvovirus[9]; ability to infect the to its size, so theoreticallyany virus can mutate rapidly,al- new species may have been conferredby a mutation in the thoughaccording to Holland,RNA virusesusually have higher capsid gene [10]. Seal plague, a newly recognized paramyx- mutationrates than do DNA viruses of the same genome size. ovirus, is related to, but distinct from, measles and canine This is generallyascribed to the lack of error-correctingmech- distemperviruses [11]. The virus may have been transferred anisms in RNA synthesis.Palese reportedhigh mutationrates directly from another species of seal [12]; possibly an out- for influenzavirus genes. The changes occurredin the non- breakof caninedistemper might have contributed to its transfer structuralprotein (NS) gene of influenzaA virus duringa sin- [13], although this is not clear. gle cycle of replicationin tissue culture. A mutationrate of MO-5 changes per nucleotide site per replicationcycle was observed[21]. Similartissue cultureexperiments revealed mu- Influenza Virus as a Model for Viral Emergence tation rates MO-fold lower (MO-6 mutations/site/cycle)for Data relatingto emergenceof pandemicstrains and genetic poliovirus [21] and 10-fold higher (M0~4 mutations/site/cy- evolutionare most extensive for influenzavirus. The proba- cle) for Rous sarcoma virus [22]. bility of interspeciestransfer can be increasednot only by in- In addition,Palese reported on the evolutionrate of influenza creasedcontact between humans and an animalreservoir but viruses. In contrastto the mutationrate, this rate describes also by increasedopportunity for viral genetic reassortment the changes observed when the viruses are passaged in hu- or recombinationwithin animal or insect hosts. Because mans. The evolution rate of the influenzaA virus NS gene influenzavirus has an eight-segmentedgenome, it has con- is 1.95 x lO-3changes/site/year, several orders of magnitude siderablefreedom for genetic reassortment.While small epi- greaterthan that of eukaryoticgenes [23]. Also, influenzaA demics may arise from mutation(antigenic drift), all known viruses generally follow an evolutionarypattern in which a humanpandemic strains have been the resultof reassortment, single lineage dominates.In contrast,coexisting lineages oc- mostly involving the hemagglutinin(H) gene. This mecha- cur in the case of influenzaC viruses [24], and their evolu- nism was probedin depthby Webster,who espoused the idea tion rate is much slower than that of the influenzaA viruses. that influenzavirus maintainedin shore and migratingbirds InfluenzaB viruses [24] also appear to have coexisting lin- infectsducks raised on farmsand reassorts in pigs, fromwhich eages, and their evolutionrate appearsto be slower thanthat new strainsemerge to infect humans[14]. Recently Scholtis- of influenzaA virusesbut distinctly faster than that of influenza sek and Naylor [15] also proposedthis agriculturalorigin for C viruses. pandemic strains. Doolittle and colleagues [20, 25] looked at the evolution- Virulentstrains of influenzavirus also can arise from a sin- ary rates of change often genes from .Overall, gle mutation, even if pandemic strains have not generally the reverse transcriptaseshowed the slowest rate of change arisen this way. For example, in 1983 a single mutation in and the outer portion of the envelopeprotein the most rapid, a relatively avirulentstrain gave rise to an H5N2 strainthat evolving three times faster. The core portion of the gag pro-

This content downloaded from 155.58.212.160 on Mon, 18 Aug 2014 21:02:31 UTC All use subject to JSTOR Terms and Conditions 4 Morse 8l Schluederberg JID 1990;162 (July) tein changed M.6 times as fast as the transcriptase,the pro- new viruses will emerge occasionally,but the stochastic and teinase 1.8times as fast, andthe 140 aminoacids at the amino multifactorialnature of viral evolution makes it difficult to terminalof gag 2.5 timesas fast. The viralproteinase is pepsin- predict such events. like, and that from humanimmunodeficiency virus (HIV) is Accordingto Doolittle, evolution is sporadic,with as similarto thatof visna virus as humanpepsin is to its fun- retrovirusesevolving at differentrates in differentsituations. gal homologue. The proteinases of HIV and HTLV-Idiffer For instance, the human endogenous retroviralelement is from one another even more than human pepsin does from sharedwith chimpanzees,indicating no changein ^ million the fungalproteinase. The retrovirusesthus are changingex- years, whereasstrains of HIV havediverged in mere decades. traordinarilyrapidly. Endogenousretroviruses carried in the germline evolveslowly The termviral genetic sequencecan be misleadingbecause comparedwith infective retroviruses.Retroviruses probably it implies a single sequence. Most species of RNA viruses arose from transposableelements and became infectious rel- actually consist of a populationof genomes showing consid- atively recently,certainly after the emergenceof vertebrates. erablevariation around a mastersequence [26,27]. The popu- Doolittlehypothesizes that exogenous retroviruses arose from lationconcept is important.In experimentalsystems, defective endogenousretroviruses that escaped one species andinfected membersof the genomicpopulation can play a significantrole anotherby horizontaltransmission. They then may integrate in viral expression [28]. into germ line cells as new endogenous retroviruses.Most endogenous retroviruseseventually become degenerate se- in the line Selective Pressures and Constraints quences accumulating germ [20]. Generationof new viralpathogens is rare,Temin concluded, What, if any, limits are placed on virus variation?Despite and usually possible only because of high mutationrates that high mutation rates and opportunitiesfor genetic reassort- permit many neutralmutations to accumulatebefore selec- ment, numerousfactors act to minimize emergence of new tive pressureforces a change. Unlike conventionalselection- influenza A epidemics, according to Murphy.Even though driven evolution, which is stepwise, this mutation-driven avianand human influenza viruses are widespread(in humans, process allows new and probablyunpredictable viral patho- an estimated 100 million yearly), pandemicinflu- gens to develop. Hence, recognition of new pathogens un- enza viruses emergeinfrequently (every 10-40 years). Power- doubtedly must await their emergence, making the time ful constraintsappear to be at work since pandemichuman requiredto note HIV unexceptionalin this regard, particu- influenzastrains vary in their H gene, with or withouta con- larly because of the special biologic challenges posed by all comitantchange in the neuraminidase,whereas the NS gene retroviruses,especially lentiviruses,which can evadethe im- and most other genes are conserved. mune system and become latent [33, 34]. Constraintson viral evolutionare not surprisingwhen one considers the selective pressuresimposed by the host at each Broader Surveillance Strategies stage of the virus life cycle [29]. Tissuetropism determinants, discussedby Fields and Shenk, include site of entry,viral at- New viruses may thereforebest be contained by special- tachmentproteins, host cell receptors,tissue-specific genetic ized surveillanceconducted by a rapidresponse team, a task elements (e.g., promoters),host cell enzymes (e.g., protein- that could most effectivelybe carriedout, accordingto Hol- ases), host transcriptionfactors, and host resistance factors land, by a single laboratorywith a worldwidefocus. Although such as age, nutrition,and immunity.Host factorscontribute it may not be practicableto conduct rigorous surveillance significantly:Sequences such as hormonallyresponsive pro- worldwide,it wouldbe worthwhilein countrieswith tropical moterelements and transcriptional regulatory factors can link rain forestsor dense populationswhere the likelihood of dis- viral expression to cell state. ease emergence is high. Hendersonsuggested developing a The interactionof virus and host is thus complex but or- network of internationallysupported health and research dered, and can be alteredby changinga varietyof conditions. centersbased in periurbanareas of majortropical cities near Unlike bacterialvirulence, which is largelymediated by bac- rain forests. Each would combine clinical, diagnostic, and terial toxins and virulence factors, viral virulence often de- epidemiologicresearch and training units. Several participants pends on host factors, such as cellular enzymes that cleave notedan increasing,and potentially critical, shortage of trained key viral molecules. Because virulence is multigenic,defects researchersand field-workersin all areas of viral and vector in almost any viral gene may attenuatea virus [30]. For ex- biology. ample, some reassortantsof avian influenzaviruses are less virulent in primatesthan are either parental strain, indicat- Approaches to Virus Detection ing that virulence is multigenic [31]. Viral and host populations can exist in equilibriumuntil Constantsurveillance is essentialto uncovernew diseases, changesin environmentalconditions shift the equilibriumand especially in cases of large outbreaks with no dramatic favorrapid evolution [32]. It seems reasonableto expect that manifestationsor very small outbreakswith serious conse-

This content downloaded from 155.58.212.160 on Mon, 18 Aug 2014 21:02:31 UTC All use subject to JSTOR Terms and Conditions JID 1990;162 (July) Emerging Viruses 5 quences but no visibility. For identifyingviruses that are in- acid probes for virus detection. In situ hybridizationof nu- creasing their range, seroepidemiology is invaluable with cleic acids in theory can detect a single cell containing the surveysof sentinel or high-riskpopulations, as discussed by target sequence, accordingto Ward.The approachhas been Shope and Evans. Examples include tracking HTLV-I[35] more valuablefor studies of pathogenesisand tissue tropism and La Crosse (Californiaencephalitis group) virus. than for primarydetection. Filter and solution hybridization Richman classified methods for virus detection as open- assaysare insensitive,requiring 100,000-500,000 targetmol- ended when they do not require foreknowledgeof the type ecules in a sample without amplification.Amplification of of virus being sought and probe-specificwhen the search is the target by the polymerase chain reaction (PCR) reduces for specific components.The majoropen-ended approaches that requirementto ^10-100 molecules. Here specificity is include virus isolation, long the "goldstandard" of , the issue. To rule out cross-contamination,it is essential to and electronmicroscopy. Both havelimitations. Besides cost use propercontrols, such as amplifyinga cellulargene (e.g., andthe need for expertise,virus isolationrequires identifica- globin) at the same time. tion of a susceptiblehost cell and a suitable markersuch as Exciting advanced technologies include optical imaging a cytopathiceffect, immunocytochemicaltest, or assay for techniquesthat permit visualization of a single integratedvi- a viral enzyme. For viruses thatcan be grownin culture,iso- ral genomeon a chromosome.Although powerful, many such lation offers great sensitivity (via biologic amplification),is techniquesrequire specialized equipmentand are limited to relativelyspecific, and providesmaterial for furthercharac- research use. More accessible to investigators in clinical terization. laboratoriesare chemiluminescencetechnologies using com- Even though electron microscopy requires special equip- pounds based on dioxetane chemistries. This methodology ment and expertise and is ratherinsensitive, it is rapid, can can increasesensitivity of any probetagged with peroxidase, be used directly with clinical materials, and can detect un- includingnucleic acid probes or enzyme immunoassaycon- knownviruses. Immuneelectron microscopyincreases sen- jugates, to ^0.1 pg (400 molecules) [40, 41]. sitivity and specificity,although high titers of virus are still required. The hepatitis A virus and rotaviruswere discov- Characterization of Emergent Viruses ered this way. Probe-specificmethodologies include detection of antigens Rapididentification of emergentdisease-causing agents is and antibodies,nucleic acids, and, less frequently,viral en- an essential featureof a responsivecontrol program. Classic zymes such as reversetranscriptase. For identificationof new virologic methods are most widely applied to characteriza- agents, antigenand antibodydetection methods (enzyme im- tion of new viral agents. Westernblotting and nucleic acid munoassay,immunofluorescence, and traditionalserologic hybridizationare regularlyused to look for viral relatedness, methodssuch as complementfixation) require good luck and while gene sequencing permits more refined comparisons. large quantitiesof antigen(e.g., discovery of hepatitisB vi- PCR is clearly becoming important. rus or parvovirusB19) or cross-reactivitywith a knownagent Computerprograms to constructphylogenetic trees help (identificationof seal plaguevirus using cross-reactionswith in determiningrelatedness of viruses by meticulouscompar- agentsresponsible for rinderpestand canine distemper).The ison of homologousgenetic sequences [42]. By this analysis, applicabilityof antigen-antibodydetection methods can be Myers concludesthat known simian immunodeficiency virus broadenedby using immune or convalescent sera to detect (SIV) strains appearmore closely related to HIV-2 than to the unknownantigens, as was done, in an importantearly ap- HIV-1.Doolittle insteadanalyzes amino acid sequencesof the plication of indirect immunofluorescence,to identify Han- viralproteins. Although many of his resultsare similarto those taan virus (and, later, Hantaan-relatedviruses) in tissues of of Myers, Doolittle believes that HIV-1and SIVagmhave a infected rodents [36], hepatitisdelta virus in liver tissues of common ancestorcloser thanHIV-2. Because the two prom- patients, and hepatitis C virus. inentmethods for determiningevolutionary relationships from Nucleic acid isolation and cloning methods for viral tree analysisdepend on properalignment of homologous se- identification,still underdevelopment, have great potential. quences,disputes revolve around interpretation of alignments. Unlimitedamounts of standardizedreagents can be prepared Computeranalysis of genetic relatednessis expectedto con- by molecular cloning and oligonucleotide synthesis. When tinueto provideimportant insights about viral evolution, aided nucleic acid sequence data are availablefor a virus, probes by the ability of powerful new techniques such as PCR to of any desired specificity can be preparedand relatednessto generateadditional sequences for comparison.Knowledge of otherviruses can be determined.As discussedby Houghton, viral evolution is clearly still in its infancy. this technologywas successfullyapplied by his groupto hep- atitis C virus [37, 38], as well as to the delta hepatitis agent, Role of Basic Research which is the firsthuman pathogen of a uniquetype consisting ofasmallRNA [39]. Biotechnologyis a dynamicfield, with advancesproviding Thereare currentlythree basic approachesto using nucleic a continuoussuccession of improvements.However, successful

This content downloaded from 155.58.212.160 on Mon, 18 Aug 2014 21:02:31 UTC All use subject to JSTOR Terms and Conditions 6 Morse 8c Schluederberg JID 1990,162 (July) application of sophisticated technologies to control viruses ble exampleof interspeciestransfer; Brian W. J. Mahy (Centersfor is restricted by our limited knowledge of many key aspects Disease Control),seal plaguevirus; Michael Houghton (Chiron Cor- of viral pathogenesis, including factors responsible for efficient poration), new hepatitisviruses; and Gerald Myers (Los Alamos National human retroviruses. person-to-person spread, and of viral immunology and im- Laboratory), Viral Evolutionwas chairedby HowardM. Temin of munogenetics. Many speakers also emphasized their concern (University Wisconsin-Madison)with speakersJohn J. Holland (Universityof for availability of adequate personnel and resources in the fu- California-SanDiego), mutationand rapid evolution of RNA viruses; ture. how viruses interact with Only by fully understanding Palese, mutation rates and evolution in influenza and other RNA their hosts can we to devise effective hope rationally preven- viruses;James H. Strauss(California Institute of Technology),recom- tive and therapeutic strategies. bination in RNA viral evolution; Russell F. Doolittle (University of California-SanDiego), evolutionof retroviruses;Brian Murphy (NIAID), factorsrestraining emergence of mutantinfluenza viruses; Acknowledgment BernardN. Fields (HarvardMedical School), viral virulence fac- We thankthe speakersand membersof the organizingcommittee tors; Thomas E. Shenk (Princeton University), tissue tropism in for their enthusiasticand generous response, including sharing of DNA viruses; and Temin, mutation-driven evolution of viral unpublisheddata. Special thanksto John R. La Montagne for es- pathogens. sential sponsorshipand indispensableenthusiasm. We thankPravin Approachesfor AssessingFactors in ViralEmergence was chaired Bhatt(Yale University), S. GaylenBradley (Medical College of Vir- by Shope with speakersShope and Alfred S. Evans (Yale Univer- ginia-VirginiaCommonwealth University), Andrea Branch (Rocke- sity), geographicfactors and transport; Thomas E. Lovejoy(Smith- feller Universityand Cornell UniversityMedical College), Sheldon sonianInstitution), global environmentalchange; Bruce F. Eldridge Cohen (National Institute of Allergy and Infectious Diseases (University of California-Davis), evolution of arthropodvectors; [NIAID]), Paul J. Edelson (Cornell University Medical College), RobertM. May (OxfordUniversity and ImperialCollege, London), HaroldGinsberg (), Edwin D. Kilboume(Mount ecology and evolutionof host-virusassociations; Douglas D. Rich- Sinai School of Medicine), Hugh Robertson(Rockefeller Univer- man (University of California-San Diego), detection systems for sity and Cornell University Medical College), and Dennis Stark viruses; David C. Ward(Yale University), new technologies for de- (Rockefeller University) for helpful advice, historians Daniel J. tecting viruses; and Donald A. Henderson(Johns Hopkins Univer- Abrams, MarilynGewirtz, and EdwardTenner (Princeton Univer- sity), surveillance systems and intergovernmentalcooperation. sity) for suggestions on historical approaches,and JeffreyL. Fox The conferenceclosed with a panel discussion chairedby Krause for editorial help. and Edwin D. Kilbourne(Mt. Sinai School of Medicine) with addi- tional discussantsAshley T. Haase (University of Minnesota) and Lederberg. Conference Program The Planningand OrganizingCommittee consisted of William P. References Allen (NIAID), RichardM. Krause (FogartyInternational Center, NIH), JohnR. La Montagne(NIAID), ThomasP. Monath(US Army 1. MorseSS. Emergingviruses. Am Soc MicrobiolNews 1989;55:358-360 MedicalResearch Institute of InfectiousDiseases), StephenS. Morse 2. LederbergJ. Medical science, infectious disease, and the unity of hu- (RockefellerUniversity [Chairperson]),Neal Nathanson (Univer- mankind. JAMA 1988;260:684-685 sity of Pennsylvania),Peter Palese (Mt. Sinai School of Medicine 3. May RM, AndersonRM. Epidemiologyand genetics in the coevolution of City Universityof New York),Ann Schluederberg(NIAID), and of parasites and hosts. Proc R Soc Lond [Biol] 1983;219:281-313 4. Anderson RM. of infectiousdiseases. Na- Robert E. Shope (Yale University). RM, May Populationbiology ture 1979;280:361-367, 455-461 After an introductionby La Montagneand consideration by Morse 5. RM, AndersonRM. Transmission of HIV . Na- of some of the raised viral and viral evolu- May dynamics questions by emergence ture 1987;326:137-142 Joshua RockefellerUniver- tionarypotential, Lederberg(President, 6. McNeill WH. Plaguesand peoples. GardenCity, NY: Doubleday,1976 was introduced Krause.The sity), the keynote speaker, by program 7. LeDuc JW,Smith GA, ChildsJE, PinheiroFP, MaizteguiJI, Niklasson consisted of four sessions. B, AntoniadesA, RobinsonDM, Khin M, ShortridgeKF, Wooster Historical Lessons on Disease Emergencewas chairedby Frank MT, Elwell MR, Ilbery PLT,Koech D, Rosa EST, Rosen L. Global Fenner (AustralianNational University)with speakersWilliam H. survey of antibodyto Hantaan-relatedviruses among peridomestic McNeill (Universityof Chicago), patternsof disease emergencein rodents. Bull WHO 1986;64:139-144 history; Robert G. Webster (St. Jude Children'sResearch Hospi- 8. Jezek Z, Fenner F. Human monkeypox. Monogr Virol 1988;17 of tal), influenza;and KarlM. Johnson(formerly Centers for Disease 9. Parrish CR. The emergence, naturalhistory and variation canine, minkand feline In: MaramoroschK, FA, Shat- Controland US Army Medical ResearchInstitute of InfectiousDis- parvoviruses. 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