Arenavirus

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Arenavirus

• Presented by
• Sue Y. Hwang

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What are the Arenaviridae?

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

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Taxonomy

• Family Arenaviridae
• Genus Arenavirus
• Subgroup (2)
• A) LCM-LASV Complex (Old World Arenaviruses)
• B) Tacaribe Complex (New World Arenaviruses)

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What viruses are included in the virus family?

• The arenaviruses are divided into two groups the
  New World or Tacaribe complex and the Old World
  or LCM/Lassa complex.
• Of the fifteen Arenaviruses known to infect
  animals, five cause disease in humans Lassa
  virus, Junin virus, Machupo virus, Guanarito
  virus, and lymphocytic choriomeningitis virus.
  All arenaviruses contain a set of internal
  cross-reacting antigens as well as
  species-specific envelope antigens.
• Source
• http//www.cdc.gov/ncidod/dvrd/spb/mnpages/dispage
  s/arena.htm

Virus Disease
Lassa virus Lassa fever
Junin virus Argentine hemorrhagic fever
Machupo virus Bolivian hemorrhagic fever
Guanarito virus Venezuelan hemorrhagic fever
Sabia Brazilian hemorrhagic fever
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Virus Morphology

• Spherical
• An average diameter of 110-130 nm
• Enveloped in a lipid membrane.
• Has grainy particles that are ribosomes acquired
  from their host cells. (derived from the Latin
  "arena," which means "sandy." )
• Their genome is composed of RNA only.
• New viral particles, called virions, are created
  by budding from the surface of their hosts cells.

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This image shows extracellular virus particles
budding from the cell surface. Magnification
approx. 12,000 times. Image courtesy Cynthia
Goldsmith, MS, Infectious Disease Pathology
Activity, DVRD, NCID, CDC.
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Genome

• Each virion contains multiple copies of genome
  (multipartite)
• Virions contain 2 nucleic acid.
• Two segments of (RNA L and S) linear
  negative-sense single stranded RNA.
• - S encodes the major structure of the
  virion (NP, GP-1, and GP-2). - L encodes the
  viral RNA-dependent RNA polymerase (L), and a
  regulatory protein (Z).
• Total genome length is 5000-7400 nt.
• Each segment forms a circle by hydrogen
  bonding of its end. (Nucleotide sequences of
  3'-terminus largely complementary to similar
  regions on the 5' end) The hairpin serves as the
  transcription termination signal.
• Genome itself is non-infectious

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

• Replication cycle is not fully understood yet.

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Replication continued

• Virions attach to undefined receptors and enter
  host cells.
• Virus uncoating occurs in the cytoplasm the
  viral nucleic acid is delivered to the cell
  cytoplasm the site of mRNA
• Early genes are expressed during genome
  uncoating.
• Transcription of the genome and replication is
  confined to the cytoplasm.
• 5. Non-structural proteins involved in
  transcription.
• -The viral genome is transcribed from the
  viral sense strand either from the 3' end or from
  the 5' end
• - By a viral RNA-dependent RNA polymerase
  into 2 mRNA(s) (S and L mRNA).

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• 6. The small (S) RNA in the virion encodes
• - in the negative sense a nucleoprotein
  (NP)
• - in the positive or message sense a
  precursor glycoprotein (GPC), which is cleaved
  into two virion glycoproteins (GP1 and GP2).
• The large (L) RNA in the virion encodes
• -in the negative sense an
  RNA-dependent RNA polymerase (L)
• -in the positive sense a zinc-binding
  protein (Z) which binds to the ribonucleoprotein
  complex.
• 7. Specific termination sequences have been
  identified. Termination is caused by
  characteristic GC-rich, strongly base-paired stem
  loop-structure.
• 8. The virus buds from the plasma membrane,
  incorporating host lipids into the virus membrane.

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• 9. Host cells remain intact. Virus is released
  from host cell by budding through the cell
  membrane and gain an envelope. Virus is released
  from host cell without causing death.

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Pathogenesis

• Chronic infection in rodent host.
• (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 to offspring
  during pregnancy. Thus, virus remains in the
  rodent population generation after generation
• 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 incidence of human cases.
• Human infection occurs by contact with rodent
  excretions
• Contaminated food
• Dust with urine (inhale)
• Exposed wounds
• Secondary spread (person-person)
• Nosocomial
• Contact with infected blood and other excretions
• Contact with contaminated medical equipment

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Pathogenesis.. continued

• Zoonotic
• (In nature, the virus is found in animals)
• Each virus is associated with either one species
  or a few closely related rodents.
• EX
• 1. Tacaribe complex viruses are associated
  with the New World rats.
• 2. The LCM/Lassa complex viruses are
  associated with the Old World rats.

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Symptoms

• The onset of the hemorrhagic fevers caused by
  Lassa, Junin, Machupo, and Guanarito viruses
• - within 7 to 14 days,
• -pyrexia
• -headache
• -sore throat
• -myalgia
• Virus can be recovered from the blood and serum
  for up to 3 weeks after onset of the infection.
• Lassa virus can be recovered from the urine for
  up to 5 weeks.

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Host Defenses

• Interferon is induced by Arenavirus infection.
• Slow humoral response.
• Cell-mediated immunity is probably of prime
  importance

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Epidemiology

• The arenaviruses that affect humans exist in
  nature as benign infections in restricted rodent
  hosts

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• Frequent hospital-acquired infections in West
  Africa brought Lassa virus to the attention of
  the medical world 25 years ago. It is transmitted
  at the village level and that most infections are
  asymptomatic. For those sick enough to be
  admitted to the hospital, mortality is about 15
  percent.
• 1. The case fatality rates associated with Junin,
  Machupo, and Guanarito viruses range from 5 to 35
  percent.
• LCM virus, which is found worldwide in Mus
  musculus (the common field mouse), is considered
  to be the agent in about 5 percent of CNS
  infections. These infections are rarely fatal.

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Diagnosis

• Differential clinical diagnosis is complex the
  diagnosis is confirmed only by detecting a rise
  in antibody titers (IgM, IgG) or by isolating the
  virus.
• The traditional methods of diagnosis
• -Virus isolation
• - Virus neutralization
• - Detection of antibodies
• - Polymerase chain reaction technology.

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Prevention

• Keep food in rodent proof containers
• Reduce rodent population
• At a hospital setting
• Wear protective clothing
• Sterilize equipment

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Treatment

• Therapy with ribavirin (anti-viral) is proven to
  be effective in treating some infections in
  Africa and South when given early in infection.
• The sooner treatment is started after infection,
  the better the chances of survival.

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Control

• Elimination of rodents is effective but often not
  practical
• Vaccines and antiviral agents
• (e.g., ribavirin)
• .

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Sources

• http//www.cdc.gov/ncidod/dvrd/spb/mnpages/dispage
  s/arena.htm
• http//www.virology.net/Big_Virology/BVRNAarena.ht
  m
• http//gsbs.utmb.edu/microbook/ch057.htm