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Arenavirus

Presented by
Sue Y. Hwang

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


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

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/dispages/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
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.
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.

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
From Ray Baumann, at the University of Mississippi School of Medicine
Replication
Replication
cycle is not
fully
understood
yet.



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

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

3. Early genes are expressed during genome uncoating.

4. 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).

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.
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.

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


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.
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.
Host Defenses

Interferon is induced by Arenavirus
infection.

Slow humoral response.

Cell-mediated immunity is probably of
prime importance
Epidemiology

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

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.
2. 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.

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.


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

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.

Control

Elimination of rodents is effective but
often not practical

Vaccines and antiviral agents
(e.g., ribavirin)
.
Sources
http://www.cdc.gov/ncidod/dvrd/spb/m
npages/dispages/arena.htm
http://www.virology.net/Big_Virology/BV
RNAarena.htm
http://gsbs.utmb.edu/microbook/ch057
.htm