Emerging viruses Lecture 22 Biology W3310/4310 Virology Spring 2015
Nothing endures but change HERACLITUS Emerging viruses
• Emerging virus - causa ve agent of a new or previously unrecognized infec on • The term became popular in 1990s, but emerging viruses are not new • Since the rise of agriculture - 11,000 years ago - new infec ous agents have invaded human popula ons because they can be sustained by numbers that were unknown before agriculture and commerce Emerging viruses
• Expanded host range with an increase in disease not previously obvious • Transmission of a virus from a wild or domes cated animal to humans - zoonosis • Cross-species infec on may establish a new virus in the popula on (SIV moving from chimps to humans) • O en cross-species infec on cannot be sustained (e.g. Ebola and Marburg from bats to humans) Human - animal interface
6
16 32 Adapted pathogens (> Homo sapiens) Zoono c pathogens Heirloom pathogens (< Homo spp.) Heirloom pathogens (> Homo spp.)
37
Viruses belonging to # of genera One Health, ASM Press
Convergent Forces of Disease Emergence
GLOBALIZATION RAPID AIR TRAVEL
ALTERED ECOSYSTEMS
EXPANDING POPULATIONS “MEGA- CITIES” POVERTY MICROBIAL EVOLUTION
DEFORESTATION ENVIRONMENTAL CHANGES Over-riding factors driving the emergence of infec ous diseases of humans and animals:
Human popula on growth and incredible change occurring in all ecosystems brought about by human occupa on of almost every corner of the planet The Amazon North Region of Brazil Home to 183 Arthropod-borne and Other Vertebrate Viruses
Cacipacore, Trombetas, Mapuera, Serra do Navio, Oriximina, Turuna, Saraca, Juruaca Araguari, Amapari, Aura, EEE, Una, WEE, Bussuquara, Ilheus, Ieri, Cupixi Kairi, Maguari, Taiassui, Caraparu, Itaqui, Munguba, Jari, Jutai, Murutucu, Nepuyo, Melao, Acara, Benevides, Monte Dourado, Paru, Benfica, Bushbush, Capim, Guajara, 0º Tumucumaque, Almeirim Ananindeua, Bimiti, Catu, Mirim, Moju, Timboteua, Utinga, Turlock, Bujaru, Icoaraci, Itaporanga, Urucuri, Belem, Para, Acado-like, Mosqueiro, Kwatta-like, Chaco, Timbo, Piry, Marco, Aruac, Inhangapi, Agua Preta, Cotia- like, Marajo, Mucambo, yellow fever, Tacaiuma, Tucunduba, Apeu, Marituba, Boa Vista Melgaco Oriboca, Caraparu-like, Guama, Anhanga, Mayaro dengue 1, dengue 4 dengue 2, dengue 3, Bocas, Triniti, Amapa Barcarena Roraima Macapa
Pixuna, SLE, Lukuni, Sororoca, Guaroa, Belem Oropouche, Candiru, Pacui, Caninde, Gurupi, Irituia, Ourem, Tembe, Cocal, Jurona
Balbina, Manaus Uatuma Para Arumateua, Caraipe,Tucurui,Guamboa-Like, Uriurana, Anapu, Aracai, Aratau, Aruana, Arawete, Bacuri, Canoal, Coari, Iopaka, Ipixaia, Iruana, Itaboca, Jandia, Jatuarana, Pacaja, Parakana, Murumbi Paranati, Pependana, Pindobai, Piratuba, Surumbi, Tekupeu, Timbozal, Tocantins, Tocaxa, Tuere, Xaraira, Xiwanga, Breu Branco, Trocara, Jatobal, Amazonas Jacunda.
Itupiranga
Palmas Porto Velho Iaco, Moriche, Acre Xingu, Ambe, Joa, Tapara, Purus, Sena Mojui dos Acatinga, Acurene, Altamira, Madureira, Campos, Santarem, Assurinis, Bacajai, Gorotire, Xiburema Rio Branco Belterra, Jamanxi Kararao, Uxituba, Cajazeira, Cuiaba, Tocantins Codajas, Galibi, Iriri, Uruara Rondonia Alenquer
Ariquemes
Atlantic Ocean Itaituba, Pacora- like, Jacareacanga, Flexal North Region South America
Serra Norte, Catete, Parauapebas, Serra Sites from which viruses were isolated at the Sul, Tapirope, Carajas, Maraba, Brazil Curianopolis, Evandro Chagas Ins tute Itacaiunas
Atlantic Ocean
0 500 1,000
Kilometers Virus Family Drivers of Emergence Urban population density, Dengue virus Flaviviridae mosquito breeding Human contact with natural Ebolavirus Filoviridae host; bushmeat Agriculture: human/rodent Hantaan virus Bunyaviridae contact Bats to horses to stable Hendra virus Paramyxoviridae workers HIV Retroviridae Bushmeat trade Influenza virus Orthomyxoviridae Pig/bird agriculture
Junin virus Arenaviridae Agriculture: human/rodent contact Nipah virus Paramyxoviridae Bats to pigs to humans
Machupo virus Arenaviridae Agriculture: human/rodent contact Rift Valley virus Bunyaviridae Dams, irrigation Weather, human/rodent Sin Nombre virus Bunyaviridae contact West Nile virus Flaviviridae Mosquito Principles of Virology, ASM Press Roles of Evolu on
• Leads to the biodiversity of pathogens exis ng in nature (quasispecies) • Adapta on to new hosts and environments (through varia on and selec on) The general interac ons of hosts and viruses
• Stable: maintains virus in ecosystem • Evolving: passage of virus to naive popula on • Dead-end: one way to different species • Resistant host: infec on blocked Principles of Virology, ASM Press Stable host-virus interac ons
• Both par cipants survive and mul ply • Some are effec vely permanent - Humans are sole natural host for measles virus, herpes simplex virus, HCMV, smallpox • May include infec on of more than one species - Influenza A virus, flaviviruses, togaviruses
Principles of Virology, ASM Press Evolving host-virus rela onship
• Hallmarks are instability and unpredictability • Outcome of infec on may range from benign to death - Introduc on of smallpox and measles to na ves of Americas by Old World colonists and slave traders - Introduc on of West Nile virus into Western Hemisphere, 1999 • Introduc on of rabbits into Australia Principles of Virology, ASM Press Dead-end interac on
• Frequent outcome of cross-species infec on • Ebolavirus: humans, chimps, gorillas • New infected host may not transmit the infec on to others of the same species (H5N1) • Contribute li le to the spread of a natural infec on
Principles of Virology, ASM Press The complex life cycle of an arbovirus
Stable host- virus interac ons
Principles of Virology, ASM Press Rodents and insect vectors move European ck-borne encephali s virus among many hosts
Dead-end hosts
Principles of Virology, ASM Press Other dead-end infec ons
• Yellow fever (monkey) • Marburg, Ebola, Hendra, Nipah, SARS progenitor (bats) • Lassa, Junin, Sin Nombre (rodents) • Laboratory animal models Emerging infec ons: Two steps
• Introduc on • Establishment and dissemina on Encountering new hosts
• Rare chance encounters of viruses with new hosts may never be detected • Single-host infec ons are not transmi ed among humans for many reasons Expanding viral niches
• Successful encounters require access to suscep ble and permissive cells • Popula on density and health are important factors • Virus popula ons will endure in nature only because of serial infec ons (a chain of transmission) Human are constantly providing new ways to meet viruses
Dams and water impoundments Irriga on Massive deforesta on Rerou ng of wildlife migra on pa erns Wildlife parks Long distance transport of livestock and birds
Air travel Uncontrolled urbaniza on Day care centers Hot tubs Air condi oning Used re trade
Blood transfusion Xenotransplanta on Sex and drug abuse
Principles of Virology, ASM Press Diseases of explora on and coloniza on
• Explosive epidemic spread may occur when a virus enters a naive popula on • Smallpox reached Europe from the Far East in 710 AD, a ained epidemic propor ons • Smallpox changed the balance of human popula ons in the New World - killed 3.5 million Aztecs in 2 years (1520 - spread from Hispaniola), allowing conquest by Cortez Yellow fever virus: Humans change the pa ern and pay the price
Yellow fever deaths, Philadelphia, 1793
“Yellow Fever will discourage the growth of great ci es in our na on” THOMAS JEFFERSON, 1800
Principles of Virology, ASM Press Changes in human popula ons and environments
• Emergence of epidemic poliomyeli s in the beginning of the 20th century: improved sanita on delayed transmission • Known since 4,000 years ago, stable host-virus rela onship Poliomyeli s: A disease of modern sanita on
Principles of Virology, ASM Press Influenza
631 deaths | 253 deaths Bats: a source of zoono c infec ons
•Many new paramyxoviruses found in flying foxes since 1995, including Nipah and Hendra viruses
•Cause severe disease in domes c animals (horses and pigs) and are known to infect humans Nipah virus • First outbreak Malaysia 1998 - Outbreak of respiratory and neurological disease on pig farms - 105 human deaths, 1 million pigs culled • Fruit bats excrete virus in urine but are unaffected • Pig farmers plant mangoes near pigpens • Pigs spread infec on to humans • Subsequently humans infected by consuming date palm sap contaminated by bats (India, Bengladesh) • Human to human transmission; infec ons con nue Hendra virus
• Discovered in Hendra, Australia, September 1994 - Outbreak killed 14 racehorses and a trainer • Spread from flying foxes to horses, then to humans • Horses con nue to acquire infec on h p://www.twiv.tv/2014/08/03/twiv-296/ Changing climate and animal popula ons
• Hantavirus pulmonary syndrome - first noted in Four Corners area of New Mexico, 1993 • Disease is caused by Sin Nombre virus, endemic in the deer mouse (Peromyscus maniculatus, 30% virus posi ve) • Originally called Muerto Canyon virus, but residents objected Changing climate and animal popula ons
• In 1992-93, abundant rainfall produced a large crop of piñon nuts, food for humans and the deer mouse. Mouse popula on rose, contact with humans increased. • Virus is excreted in mouse feces; contaminated blankets or dust from floors provided opportuni es for human infec on • Humans not the natural host for Sin Nombre virus, human disease is rare • Not new - earliest known case 1959 Deer mouse, white-footed mouse, rice rat, co on rat
New World Hantaviruses New York Sin Nombre Peromyscus leucopus Peromyscus maniculatus Prospect Hill Muleshoe Microtus pennsylvanicus Sigmodon hispidus Bloodland Lake Microtus ochrogaster Isla Vista Bayou Microtus californicus Oryzomys palustris Black Creek Canal El Moro Canyon Sigmodon hispidus Reithrodontomys megalo s Rio Segundo Calabazo Reithrodontomys mexicanus Zygodontomys brevicauda Juqui ba Caño Delgadito Unknown Host Laguna Negra Choclo Sigmodon alstoni Calomys laucha Oligoryzomys fulvescens Rio Mamore Maciel Oligoryzomys micro s Necromys benefactus Orán Hu39694 Oligoryzomys longicaudatus Unknown Host Bermejo Lechiguanas Oligoryzomys chacoensis Oligoryzomys flavescens Pergamino Andes Akodon azarae Oligoryzomys longicaudatus
(Virus Names in Orange are Associated with Human Disease) SARS
• Outbreak of severe atypical pneumonia, unknown e ology, Guangdong Province, China, Nov 2002 - 305 cases, 5 deaths • Incuba on period 2-10 days • Illness begins with prodrome of fever - Chills, headache, malaise, myalgia • Next phase: dry cough, shortness of breath • 10-20% may require mechanical ven la on SARS (Severe acute respiratory syndrome)
• A Chinese doctor who treated first pa ents traveled to Hong Kong on 21 February 2003, stayed on ninth floor of Metropole Hotel • He died in hospital 22 February • Infec on spread to 10 people in hotel, who flew to Singapore, Vietnam, Canada, US before symptoms evident • Infec on spread to 8000 people in 29 countries, 10% mortality Spread from Hotel Metropole (21 February 2003) 249 cases traced to “A” as of March 28, 2003
Canada Guangdong F,G 18 HCW Province, China A F,G 11 close contacts
A Ireland K K A Hotel M 0 HCW Hong Kong Hong Kong SAR H,J I, L,M Hosp. 1: 99 HC H,J 8 hospitals total B C,D,E
Total: 156 close contacts of I,L,M HCW and pa ents B C,D,E United States Vietnam Singapore 1 HCW 37 HCW 34 HCW
21 close contacts 37 close contacts Probable cases of SARS by date of onset, Hong Kong: n = 1 753, as of 9 June 2003 120
100
80
60
Number of cases 40
Outbreak ends July 2003 20
0 0 1 Feb 13 Feb 25 Feb 9 Mar 21 Mar 2 Apr 14 Apr 26 Apr 8 May 20 May 1 Jun 9 Jun Probable SARS Cases Worldwide Reported to WHO as of Sept. 26, 2003
Europe: 10 countries (34) Canada (251) China (5327)
U.S. (29) Hong Kong (1755)
Taiwan (346) Vietnam (63)
Singapore (238 + 1)
Thailand (9) Australia (6)
Total: 8,098 cases; 774 deaths (9.6% case fatality) SARS-coronavirus
SARS virion ~120 nm SARS-CoV disease mechanisms
• Transmi ed by respiratory droplets • Virus enters respiratory tract and mul plies in epithelial cells • Mul plica on in alveolar epithelial cells leads to lung injury • Immune suppression cause of severe disease?
Principles of Virology, ASM Press SARS and the economy: impact on global travel Airport screening and health informa on, Hong Kong, SARS, 2003 Origin of SARS-CoV • Human sera collected before SARS outbreak do not contain an bodies to SARS-CoV • Early Guangdong SARS cases were in handlers of animals for the exo c food market • Animal traders had significantly higher prevalence of an -SARS- CoV an bodies than control groups Origin of SARS-CoV
• SARS-like CoVs isolated from different species of horseshoe bats in regions of China >1000 km apart • Up to 84% of bats examined had an -SARS-CoV an bodies • Bat SARS-like-CoVs 88-92% sequence iden ty with human or civet strains • Greater gene c diversity in bat viruses than those of humans or civets • Hypothesis: bats are reservoir of SARS-CoV, transmi ed to humans via market animals (e.g. civets) Will SARS Return?
CREDIT: MICHAEL REYNOLDS/EPA/NEWSCOM
• No further transmission of human SARS-CoV • December 2003 - January 2004: 4 SARS cases in Guangdong Province, new animal - human transmission • SARS-CoV precursor con nues to circulate in animals; wild game banned in markets • Re-emergence will be more quickly recognized and contained MERS-CoV
• Index case September 2012: 60 yo male pa ent, died of pneumonia, renal failure • Virus recovered, genome sequenced, binds dipep dyl pep dase 4 receptor • Closely related to bat coronaviruses • Not SARS-CoV h p://www.who.int/csr/disease/coronavirus_infec ons/archive_updates/en/ h p://www.who.int/csr/disease/coronavirus_infec ons/archive_updates/en/ MERS-CoV
• As of 4/16/15: 1106 laboratory confirmed cases, 421 deaths • Case fatality ra o: 421/1106 = 38% • Mortality ra o unknown MERS-CoV in dromedary camels
An bodies in serum PCR posi ve nasal swab MERS-CoV
• Are camels the reservoir? • Why did the virus recently cause human disease? • What is the role of bats if any? • How is the virus transmi ed to humans? • Why are so few humans infected? Will it spread? • Why doesn’t the virus transmit well among humans? • Should a camel vaccine be prepared? • Should we produce an virals for infected pa ents? Coronavirus disease in humans
Virus Disease 1686 - 1800, bat CoV HCoV-229E •Respiratory diseases 1450 - 1191, bat CoV HCoV-NL63 • Febrile upper tract infec on 1890, bovine CoV HCoV-OC43 • Lower tract infec ons HCoV-HKU1 • Asthma exacerba on 2003, bat CoV SARS-CoV • Atypical pneumonia 2012, camel CoV MERS-CoV • Severe pneumonia Canine parvovirus: Cat-to-dog by two muta ons
• Canine parvovirus iden fied in 1978, cause of new enteric and myocardial infec on in dogs • Evolved from feline panleukopenia virus, another parvovirus - Infects cat, mink, racoon Canine parvovirus
two amino acid changes!
Interna onal travel allowed stable virus to be carried on contaminated footwear, not in infected dogs How common are host range jumps?
• Dead end: Very common • Those that produce sustaining transmission: Rare • Can we predict them? No • But we can know what is out there, and react (preparedness)