ArenavirusArenavirus

Presented byPresented by

Sue Y. HwangSue Y. Hwang

What are the What are the Arenaviridae?Arenaviridae? Arenaviridae Arenaviridae

* A family of viruses whose members * A family of viruses whose members are generally associated with rodent-are generally associated with rodent-transmitted disease in humans. transmitted disease in humans.

TaxonomyTaxonomy

FamilyFamily: Arenaviridae: Arenaviridae GenusGenus: Arenavirus: Arenavirus Subgroup (2):Subgroup (2): A) LCM-LASV Complex (Old World ArenaviruA) LCM-LASV Complex (Old World Arenaviru

ses) ses) B) Tacaribe Complex (New World ArenaviruB) Tacaribe Complex (New World Arenaviru

ses)ses)

What viruses are included What viruses are included in the virus family?in the virus family?

The arenaviruses are divided into tThe arenaviruses are divided into two groups: the New World or Tacarwo groups: the New World or Tacaribe complex and the Old World or Libe complex and the Old World or LCM/Lassa complex. CM/Lassa complex.

Of the fifteen Arenaviruses known to infect aOf the fifteen Arenaviruses known to infect animals, five cause disease in humans: Lassnimals, five cause disease in humans: Lassa virus, Junin virus, Machupo virus, Guanarita virus, Junin virus, Machupo virus, Guanarito virus, and lymphocytic choriomeningitis viruo virus, and lymphocytic choriomeningitis virus. All arenaviruses contain a set of internal cs. All arenaviruses contain a set of internal cross-reacting antigens as well as species-spross-reacting antigens as well as species-specific envelope antigens. ecific envelope antigens.

Source:Source: http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/arena.htmhttp://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/arena.htm

VirusVirus DiseaseDisease

Lassa virus Lassa virus Lassa feverLassa fever

Junin virus Junin virus Argentine hemorrhagic feverArgentine hemorrhagic fever

Machupo virusMachupo virus Bolivian hemorrhagic fever Bolivian hemorrhagic fever

Guanarito virusGuanarito virus Venezuelan hemorrhagic feverVenezuelan hemorrhagic fever

SabiaSabia Brazilian hemorrhagic feverBrazilian hemorrhagic fever

Virus MorphologyVirus Morphology SphericalSpherical An average diameter of 110-130 nmAn average diameter of 110-130 nm Enveloped in a lipid membrane. Enveloped in a lipid membrane. Has grainy particles that are ribosomes Has grainy particles that are ribosomes

acquired from their host cells. (derived from acquired from their host cells. (derived from the Latin "arena," which means "sandy." )the Latin "arena," which means "sandy." )

Their genome is composed of RNA only.Their genome is composed of RNA only. New viral particles, called virions, are New viral particles, called virions, are

created by budding from the surface of created by budding from the surface of their hosts’ cells.their hosts’ cells.

This image shows extracellular virus particles budding from the cell surface. This image shows extracellular virus particles budding from the cell surface. Magnification approx. 12,000 times. Magnification approx. 12,000 times.

Image courtesy Cynthia Goldsmith, MS, Infectious Disease Pathology Activity, DVRD, NCID, CDC.Image courtesy Cynthia Goldsmith, MS, Infectious Disease Pathology Activity, DVRD, NCID, CDC.

GenomeGenomeEach virion contains multiple copies of genome (multipartite)Each virion contains multiple copies of genome (multipartite)

Virions contain 2 % nucleic acid. Virions contain 2 % nucleic acid. * Two segments of (RNA L and S) linear negative-sense * Two segments of (RNA L and S) linear negative-sense

single stranded RNA.single stranded RNA. - S encodes the major structure of the virion- S encodes the major structure of the virion

(NP, GP-1, and GP-2). (NP, GP-1, and GP-2). - L encodes the viral RNA-dependent RNA polymerase (L), - L encodes the viral RNA-dependent RNA polymerase (L), and a regulatory protein (Z). and a regulatory protein (Z).

Total genome length is 5000-7400 nt.Total genome length is 5000-7400 nt. * Each segment forms a circle by hydrogen bonding of its * Each segment forms a circle by hydrogen bonding of its

end. (Nucleotide sequences of 3'-terminus largely end. (Nucleotide sequences of 3'-terminus largely complementary to similar regions on the 5' end) The hairpin complementary to similar regions on the 5' end) The hairpin serves as the transcription termination signal. serves as the transcription termination signal.

* Genome itself is non-infectious * Genome itself is non-infectious

From From Ray BaumannRay Baumann, at the University of Mississippi School of Medicine, at the University of Mississippi School of Medicine

ReplicationReplication

Replication Replication cycle is not cycle is not fully fully understood understood yet.yet.

....

Replication continuedReplication continued1.1. Virions attach to undefined receptors and enter host cells.Virions attach to undefined receptors and enter host cells.

2.2. Virus uncoating occurs in the cytoplasm; the viral nucleic acid is dVirus uncoating occurs in the cytoplasm; the viral nucleic acid is delivered to the cell cytoplasm; the site of mRNA elivered to the cell cytoplasm; the site of mRNA

3.3. Early genes are expressed during genome uncoating. Early genes are expressed during genome uncoating.

4.4. Transcription of the genome and replication is confined to the cytoTranscription of the genome and replication is confined to the cytoplasm.plasm.

5. Non-structural proteins involved in transcription. 5. Non-structural proteins involved in transcription. -The viral genome is transcribed from the viral sense stran-The viral genome is transcribed from the viral sense stran

d either from the 3' end or from the 5' endd either from the 3' end or from the 5' end - By a viral RNA-dependent RNA polymerase into 2 mRNA- By a viral RNA-dependent RNA polymerase into 2 mRNA

(s) (S and L mRNA).(s) (S and L mRNA).

6. The small (S) RNA in the virion encodes 6. The small (S) RNA in the virion encodes - in the negative sense a nucleoprotein (NP)- in the negative sense a nucleoprotein (NP) - in the positive or message sense a precursor glycoprotein - in the positive or message sense a precursor glycoprotein

(GPC), which is cleaved into two virion glycoproteins (GP1 and GP2). (GPC), which is cleaved into two virion glycoproteins (GP1 and GP2).

The large (L) RNA in the virion encodesThe large (L) RNA in the virion encodes -in the negative sense an RNA-dependent RNA polymerase (L)-in the negative sense an RNA-dependent RNA polymerase (L) -in the positive sense a zinc-binding protein (Z) which binds to th-in the positive sense a zinc-binding protein (Z) which binds to th

e ribonucleoprotein complex. e ribonucleoprotein complex.

7. Specific termination sequences have been identified. Termination is 7. Specific termination sequences have been identified. Termination is caused by characteristic GC-rich, strongly base-paired stem loop-strcaused by characteristic GC-rich, strongly base-paired stem loop-structure. ucture.

8. The virus buds from the plasma membrane, incorporating host lipid8. The virus buds from the plasma membrane, incorporating host lipids into the virus membrane.s into the virus membrane.

9. Host cells remain intact. Virus is released 9. Host cells remain intact. Virus is released from host cell by budding through the cell from host cell by budding through the cell membrane and gain an envelope. Virus is rmembrane and gain an envelope. Virus is released from host cell eleased from host cell without causing deawithout causing deathth. .

Pathogenesis Pathogenesis Chronic infection in rodent host.Chronic infection in rodent host.

(However, the viruses do not appear to cause obvious illness in them.)(However, the viruses do not appear to cause obvious illness in them.)

– Rodents that carry the Old World arenaviruses can transmit the virus from mother Rodents that carry the Old World arenaviruses can transmit the virus from mother to offspring during pregnancy. Thus, virus remains in the rodent population generato offspring during pregnancy. Thus, virus remains in the rodent population generation after generationtion after generation

– New World arenavirus carrying rodents can only transmit among adult rodents, so New World arenavirus carrying rodents can only transmit among adult rodents, so only a portion of mice are infected at one time. This leads to cyclic trends in the ionly a portion of mice are infected at one time. This leads to cyclic trends in the incidence of human cases.ncidence of human cases.

Human infection occurs by contact with rodent excretionsHuman infection occurs by contact with rodent excretions– Contaminated foodContaminated food– Dust with urine (inhale)Dust with urine (inhale)– Exposed woundsExposed wounds

Secondary spread (person-person)Secondary spread (person-person)– NosocomialNosocomial– Contact with infected blood and other excretionsContact with infected blood and other excretions– Contact with contaminated medical equipmentContact with contaminated medical equipment

Pathogenesis.. continuedPathogenesis.. continued

ZoonoticZoonotic(In nature, the virus is found in animals) (In nature, the virus is found in animals)

Each virus is associated with either one species or a few Each virus is associated with either one species or a few closely related rodents. closely related rodents.

EX:EX: 1. Tacaribe complex viruses are associated with the Ne1. Tacaribe complex viruses are associated with the Ne

w World rats.w World rats. 2. The LCM/Lassa complex viruses are associated with 2. The LCM/Lassa complex viruses are associated with

the Old World rats. the Old World rats.

SymptomsSymptoms The onset of the hemorrhagic fevers caused by Lassa, JuThe onset of the hemorrhagic fevers caused by Lassa, Ju

nin, Machupo, and Guanarito viruses:nin, Machupo, and Guanarito viruses: - within 7 to 14 days, - within 7 to 14 days, -pyrexia-pyrexia -headache-headache -sore throat-sore throat -myalgia-myalgia

Virus can be recovered from the blood and serum for up to Virus can be recovered from the blood and serum for up to 3 weeks after onset of the infection.3 weeks after onset of the infection.

Lassa virus can be recovered from the urine for up to 5 weLassa virus can be recovered from the urine for up to 5 weeks. eks.

Host Defenses Host Defenses

Interferon is induced by Arenavirus Interferon is induced by Arenavirus infection. infection.

Slow humoral response. Slow humoral response.

Cell-mediated immunity is probably Cell-mediated immunity is probably of prime importance of prime importance

Epidemiology Epidemiology

The arenaviruses that The arenaviruses that affect humans exist in affect humans exist in nature as benign infecnature as benign infections in restricted rodtions in restricted rodent hostsent hosts

Frequent hospital-acquired infections in West Africa brouFrequent hospital-acquired infections in West Africa brought Lassa virus to the attention of the medical world 25 yght Lassa virus to the attention of the medical world 25 years ago. It is transmitted at the village level and that moears ago. It is transmitted at the village level and that most infections are asymptomatic. For those sick enough to st infections are asymptomatic. For those sick enough to be admitted to the hospital, mortality is about 15 percenbe admitted to the hospital, mortality is about 15 percent. t.

1. The case fatality rates associated with Junin, Machupo, a1. The case fatality rates associated with Junin, Machupo, and Guanarito viruses range from 5 to 35 percent.nd Guanarito viruses range from 5 to 35 percent.

2.2. LCM virus, which is found worldwide in LCM virus, which is found worldwide in Mus musculus Mus musculus (th(the common field mouse), is considered to be the agent in e common field mouse), is considered to be the agent in about 5 percent of CNS infections. These infections are rabout 5 percent of CNS infections. These infections are rarely fatal. arely fatal.

Diagnosis Diagnosis

Differential clinical diagnosis is complex; the Differential clinical diagnosis is complex; the diagnosis is confirmed only by detecting a rise in diagnosis is confirmed only by detecting a rise in antibody titers (IgM, IgG) or by isolating the virus.antibody titers (IgM, IgG) or by isolating the virus.

The traditional methods of diagnosis:The traditional methods of diagnosis:

-Virus isolation-Virus isolation

- Virus neutralization- Virus neutralization

- Detection of antibodies- Detection of antibodies

- Polymerase chain reaction technology. - Polymerase chain reaction technology.

PreventionPrevention

Keep food in rodent prKeep food in rodent proof containersoof containers

Reduce rodent populaReduce rodent populationtion

At a hospital settingAt a hospital setting– Wear protective clothinWear protective clothin

gg– Sterilize equipmentSterilize equipment

TreatmentTreatment

Therapy with ribavirin (anti-viral) is proven to bTherapy with ribavirin (anti-viral) is proven to be effective in treating some infections in Africa e effective in treating some infections in Africa and South when given early in infection.and South when given early in infection.

The sooner treatment is started after infectioThe sooner treatment is started after infection, the better the chances of survival.n, the better the chances of survival.

Control Control

Elimination of rodents is effective but often Elimination of rodents is effective but often not practicalnot practical

Vaccines and antiviral agents Vaccines and antiviral agents (e.g., ribavirin) (e.g., ribavirin) ..

SourcesSources

http://www.http://www.cdccdc..govgov//ncidodncidod//dvrddvrd//spbspb//mnpagesmnpages//dispagesdispages/arena./arena.htmhtm

http://www.virology.net/Big_Virology/BVRhttp://www.virology.net/Big_Virology/BVRNAarena.htm NAarena.htm

http://gsbs.utmb.edu/microbook/ch057.hhttp://gsbs.utmb.edu/microbook/ch057.htmtm