12 Chapter 38 Rodent

8/10/2019 12 Chapter 38 Rodent

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Rodent-Borne Viral Diseases Rodents act as both vector and reservoir

Usually nonpathogenic in rodents Viruses often speciate with their rodent reservoirs Two principal groups

Bunyaviruses

Hantaviruses Arenaviruses


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Hantaviruses Family Bunyaviridae Genus Hantavirus Negative sense ssRNA Tripartite segmented genome

S = nucleocapsid

M = Gn/Gc glycoproteins L = RNA polymerase

Enveloped 70 nm particles


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Hantavirus Transmission Cycle

Spillover fromaerosolized

excreta

HorizontalTransmission

UrineFeces

Throat swabBlood (acute)

Hantaviruses probably originatedin shrews, moles or bats,

then jumped to rodents and diverged


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Hantavirus Disease(Pre-1993)

Nephritis

Eurasia

Ancient China

WWI

WW2

Korean War

Virus isolation 1976 ( Hantaan virus)

100,000 to 200,000 cases each year (5% mortality)


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First recognized in 1993 Four-Corners outbreak Specific to the Americas Acute febrile illness associated with headache, malaise and

myalgia Progression to ARDS within 4-6 days characterized by

thrombocytopenia, pulmonary edema, dyspnea and hypoxia

36% fatality rate due to cardiovascular shock Rapid, dramatic clinical progression Viral target: capillary endothelial cells Supportive care

Extracorporeal membrane oxygenation (ECMO) Relieves stress on heart

Hantavirus CardiopulmonarySyndrome


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U. S. Distribution of Hantavirus Cases


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Colorado Hantavirus Cases67 cases, 25 fatal, through 2009

NonfatalFatal

County


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New World Hantaviruses

Sin NombreSin Nombre Peromyscus maniculatus

Rio SegundoRio Segundo Reithrodontomys mexicanus Reithrodontomys mexicanus

El Moro CanyonEl Moro Canyon Reithrodontomys megalotis Reithrodontomys megalotis

AndesAndesOligoryzomys longicaudatusOligoryzomys longicaudatus

BayouBayouOryzomys palustrisOryzomys palustris

Black Creek CanalBlack Creek CanalSigmodon hispidusSigmodon hispidus

Rio MamoreRio MamoreOligoryzomys microtisOligoryzomys microtis

Laguna NegraLaguna NegraCalomys lauchaCalomys laucha

MuleshoeMuleshoeSigmodon hispidus

New York New York Peromyscus leucopus Peromyscus leucopus

JuquitibaJuquitibaUnknown HostUnknown Host

MacielMaciel Necromys benefactus Necromys benefactusHu39694Hu39694Unknown HostUnknown Host

LechiguanasLechiguanasOligoryzomys f lavescensOligoryzomys f lavescens

PergaminoPergamino Akodon azarae Akodon azarae

OrOr nnOligoryzomys longicaudatusOligoryzomys longicaudatus

CC a a o Delgaditoo DelgaditoSigmodon alstoniSigmodon alstoni

Isla VistaIsla Vista Microtus californicus

Bloodland LakeBloodland Lake Microtus ochrogaster Microtus ochrogaster

Prospect HillProspect Hill Microtus pennsylvanicus Microtus pennsylvanicus

BermejoBermejoOligoryzomys chacoensisOligoryzomys chacoensis

CalabazoCalabazo Zygodontomys brevicauda Zygodontomys brevicauda

ChocloChocloOligoryzomys fulvescensOligoryzomys fulvescens

CDC Websit e


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Sigmodontinae

Arvicolinae

Murinae

Hantavirus RodentReservoirsHantaan ( Apodemus agrarius ; East Asia)

Seoul ( Rattus rattus ; East Asia)

Thailand ( Bandicotta indica ; Thailand)Dobrava ( Apodemus flavicollis ; Slovenia)

Puumala ( Clethrionomys galreolus ; Northern Euope)

Tula ( Microtus arvalis ; Czech/Slovakia)

Prospect Hill ( Microtus pennsylvanicus ; MD-USA)Black Creek Canal ( Sigmodon hispidus ; FL-USA)Bayou ( Oryzomys palustris ; SE-USA)

Hu39694 (unknown; Argentina)

Lechiguanas ( Oligoryzomys flavescens ; Argentina) Andes ( Oligoryzomys longicaudatus ; Argentina)

Laguna Negra ( Calomys laucha ; Paraguay/Bolivia)Sin Nombre ( Peromyscus maniculatus ; W-USA)

New York ( Peromyscus leucopus ; NE-USA)

El Moro Canyon ( Reithrodontomys megalotis ; W-USA/N-Mexico)


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Interleukin-1 Interleukin-2 Interleukin-4 Interferon- Tumor necrosis

factor Lymphotoxin

The Role of Cytokines inPulmonary Hantavirus Infections

Pro-inflammatory

No direct viral cytopathology

Cytokine-mediated immunopathology


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Proliferation of Deer Mouse T Cells toSNV

KLH-specific T cells(uninfected deer mice)

SNV N-Ag-specific T cells(infected deer mice)

Acute InfectionKLH-specific T cells

(uninfected deer mice)

SNV N-Ag-specific T cells(infected deer mice)

Persistent Infection


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Culture for Cytokine Gene Expression

T cells APC

T cells APC

Viral Antigen

For each rodent

Extract RNA, comparegene-specific cDNA

levels by real-time PCR

(ratio)

2 days

C ki P fil f D M T


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Persistently-infected

Cytokine Profiles of Deer Mouse TCells Acutely-infected

* * * *

*

* p


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HumansVirus in lungs

No viral CPEPronounced pulmonaryinflammation Infected Cells

Capillary endothelial

Dendritic cells?Leukocyte infiltrates

T cellsMacrophages

Inflammatory cytokines

Respiratory insufficiencyNeutralizing Ab36% fatal (U. S.)

Humans vs. Rodents Rodent hosts

Virus in lungs No viral CPE No pulmonary inflammation Infected Cells

Capillary endothelial No pulmonarymononuclear infiltrates Cytokines? TGFb (Treg cells) Cell phenotypes? No respiratory insufficiency Neutralizing Ab No death

Chronic carrier


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Arenaviruses Family Arenaviridae

Single-stranded ambisense RNA 90 nm diameter Two gene segments

S - nucleocapsid, gp1, gp2

L - RNA polymerase Enveloped


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Arenaviruses

Virus Distribution Disease

Lymphocytic choriomeningitis virus global mild to severe (meningitis)

Lassa virus * West Africa Severe, often fatal (Lassa fever)

Lujo virus * South Africa Severe, often fatal hemorrhagicfever

Junin virus * ArgentinaSevere, often fatal (Argentine

hemorrhagic fever)

Machupo virus * Bolivia Severe, often fatal (Bolivianhemorrhagic fever)

Chapare virus * Bolivia Severe, often fatal (Bolivianhemorrhagic fever)

Guanarito virus * Venezuela Severe, often fatal (Venezuelan

hemorrhagic fever)Tacaribe virus Caribbean, Florida Mild febrile illness

Pichinde virus Colombia None known

Whitewater arroyo virus Western United States Hemorrhagic fever, sometimesfatal

*Category A and Select Agent


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Lassa Virus First diagnosed in late 1960s

Two missionary nurses Lassa, Nigeria

Reservoir is Mastomys spp. rodents Epidemiology

About 200,000 cases per year About 5,000 fatalities per year Some evidence of person-to-person transmission

Lassa Fever (hemorrhagic fever)

Body aches, chest pain, vomiting, cough, fatigue Hypotension , pleural effusions, proteinuria, hearing loss in some

survivors Higher fatality rate in pregnant women

Fetal death in 95% of infections


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Lassa Virus

Animal model for Lassa fever: Pirital virus in hamsters Virus isolated from Alston's cotton rat ( Sigmodon alstoni ) in

Guanarito, Venezuela (1994) BSL-3 agent Disease progression

All dead days 7-9 Hemorrhages in lungs Pneumonia Pulmonary necrosis Splenic necrosis Lymphocyte depletion Mild myocarditis Hepatomegaly Hepatic necrosis

Candidate vaccine available

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12 Chapter 38 Rodent