Hanta Virus

BY: JOHN MATTHEW TAN

SUBMITTED TO: MISS VICTORIA
SUSTENTO, RMT, MED BIO

Classification
Group:

Group 5 (negative,

ssRNA)
Order: Unassigned
Family: Bunyaviridae
Genus: Hantavirus

Morphology

Virion shape: Spherical enveloped particles with a fringe of

projection

Helical nucleocapsids

Diameter 90-110 nm

Genome shape: Linear single-stranded RNA, negative sense

3 genome segments:

S, 1-3 kb codes for Nucleocapsid protein (N protein)

M, 3-5 kb codes for 2 viral envelope glycoproteins (Gn protein, Gc protein), cleaved
from a precursor during translation

 Total

genome length 11-19 kb

These

genome segments are

encapsidated by the nucleocapsid
(N) protein to form ribonucleotide
complexes with helical symmetry.

Replication
Cytoplasmic

site of replication

1.

Virus attaches to host receptors through

Gn-Gc glycoprotein dimer.

2.

Virus is endocystosed into vesicles in

the host cell.(Beta-3 integrins mediate the
entry, found on integral cell-surface
proteins)

3. Uncoating occurs when endosomes become

acidified (pH=5-6), initiating fusion of the viral
membrane and endosomal membrane, followed by
the release of nucleocapsids into the cytoplasm
by pH-dependent fusion of the virion with the
endosomal membrane.
4. Transcription of viral genome segments into
messenger RNAs using a virion-associated L
protein. In addition to transcriptase and replicase
functions, the viral L protein is also thought to have
an endonuclease activity that cleaves cellular
messenger RNAs (mRNAs) for the production of
capped primers used to initiate transcription of viral
mRNAs;mRNAs are capped.

5. The viral S and L mRNAs are thought to undergo

translation at free ribosomes, whereas the M
mRNA is translated in the endoplasmic reticulum.
6. G1 and G2 glycoproteins form heterodimers
and are then transported from the endoplasmic
reticulum to the Golgi complex, where
glycosylation is completed.
7. The L protein produces nascent genomes by
replication via a positive-sense RNA
intermediate.

8. Hantavirions are believed to form by association

of nucleocapsids with glycoproteins
embedded in the membranes of the Golgi,
followed by budding into the Golgi cisternae.
9. Nascent virions are then transported in secretory
vesicles to the plasma membrane and released
by exocytosis.

Pathogenesis

Sin Nombre(New World Hantavirus) causes

Hantavirus pulmonary syndrome (HPS) mortality rate of 50%

Symptoms develop between 1- 5 weeks after

exposure to fresh urine, droppings, or saliva or
infected rodents

Early symptoms (about half of

all HPS patients experience
these symptoms)

Fatigue

Fever

Muscle aches especially in

thighs, hips, back &
sometimes shoulders

Headaches

Dizziness

Chills

Abdominal problems such as

nausea, vomiting, diarrhea,
and abdominal pain.

Late symptoms (4- 10

days after initial phase of
illness, late symptoms
appear- cardiopulmonary
phase)

Coughing

Shortness of breath

Pulmonary edema

Mode of Transmission
airborne
rodent

route (mainly)

bite (rare)

contact

on contaminated surfaces
then touch their nose or mouth

food

contaminated by urine, scat,

saliva from infected rodent.

Endothelial cells are the primary target host cells for

hantaviruses.Vascular permeability is increased in both
pathogenic forms of the disease, and is a key feature of the
pathogenesis of these viruses. Infected endothelial cells lack
any morphologic changes and show no visible cytopathic
effects (CPE).

Hantaviruses cause changes in the function of infected

endothelial cells that normally regulate fluid barrier
functions. The endothelium of arteries, veins, and
lymphatic vessels are unique and central to the function of
vast pulmonary capillary beds that regulate pulmonary fluid
accumulation.

 Saaremaa,

Hantaan virus, Seoul virus ,

Puumala virus, Dobrava virus(Old World
Hantaviruses) causes hemorrhagic fever
with renal syndrome- mortality rate of
1-15%.

Causes

interstitial nephritis that can lead

to acute renal insufficiency and renal
failure in severe forms.

Symptoms

of HFRS usually develop within

1 to 2 weeks after exposure to infectious
material, but in rare cases, they may take
up to 8 weeks to develop.

Initial symptoms (febrile phase)

begin suddenly and include
intense headaches, back and
abdominal pain, fever, chills,
nausea, and blurred vision.
Individuals may have flushing of
the face, inflammation or
redness of the eyes, or a rash.

Later symptoms (oliguric phase)

can include low blood pressure,
acute shock, vascular leakage,
and acute kidney failure, which
can cause severe fluid overload.

Mode of
Transmission:

Same as the HPS

Comparison of HFRS and HPS

Feature

HFRS

HPS

Major target
organ

Kidney

Lung

First phase

Febrile

Febrile prodrome

Second phase

Shock

Shock, pulmonary
edema

Evolution

Oliguria, diureses,
convalescence

Diureses,
convalescence

Mortality

1-15%

50%

Yellow-necked Mouse- Dobrava

virus

Striped field mouse- Hantaan virus

Common rat, street rat, sewer ratSeoul virus

Deer mouse- Sin Nombre virus

Laboratory Diagnosis

RT-PCR
Reverse transcriptase-PCR (RT-PCR) can be used to
detect hantaviral RNA in fresh frozen lung tissue, blood
clots, or nucleated blood cells. However, RT-PCR is very
prone to cross-contamination and should be considered an
experimental technique.
Oligonucleotide primers were designed on the basis of
regions of the M segment (G2 coding region) conserved
among hantaviruses and were used in a nested RT-PCR
assay to amplify hantavirus-specific DNA fragments from
RNA extracted from the tissues of patients.

Immunohistochemistry
IHC testing of formalin-fixed tissues with specific
monoclonal and polyclonal antibodies can be used to detect
hantavirus antigens and has proven to be a sensitive
method for laboratory confirmation of hantaviral infections.
IHC has an important role in the diagnosis of HPS in
patients from whom serum samples and frozen tissues are
unavailable for diagnostic testing and in the retrospective
assessment of disease prevalence in a defined geographic
region.

Hematology

CBC in cardiopulmonary phase

Peripheral smear demonstrates

thrombocytopenia associated with
prolonged tachypnea

Myelocytosis >10% lymphocytes with

immunoblastic morphology.

Serological Assays

ELISA
Detect IgM antibodies to the virus and to diagnose
acute infections with other hantaviruses. This assay is also
available in some state health laboratories. An IgG test is
used in conjunction with the IgM-capture test. Acute- and
convalescent-phase sera should reflect a four-fold rise in
IgG antibody titer or the presence of IgM in acute-phase
sera to be diagnostic for hantaviral disease.

Western blot assay

Using recombinant antigens and isotypespecific conjugates for IgM-IgG differentiation has
also been developed and its results are generally
in agreement with those of the IgM-capture
format.

Rapid Immunoblot strip assay (RIBA)

Investigational prototype assay to identify
serum antibody to recombinant proteins and
peptides specific for SNV and other hantaviruses.

Neutralizing plaque assay

Serological confirmation of hantaviral infection

References

Brooks, Geo et al. (2013). Jawetz, Melnick, &

Adelberg's Medical Microbiology, 26th ed. McGrawHill Companies, Inc.

Acheson, N. (2011). Fundamentals of Molecular

Virology, 2nd ed. Hoboken, NJ : John Wiley & Sons

Wallace, R. et al. (2008). Wallace/Maxcy-RosenauLast Public Health & Preventive Medicine, 15th ed.
New York : McGraw-Hill Medical

http://viralzone.expasy.org/all_by_species/82.html

http://www.bunyavirus.org/?page_id=295

http://www.infectionlandscapes.org/2012/09/hantavi
ruses.html

http://www.cdc.gov/hantavirus/technical/hanta/virolo
gy.html