Hantavirus Pulmonary Syndrome (HPS) Presentation
Brandon Thomas Suit
Hantavirus Pulmonary Syndrome
- Hantavirus was originally given attention during the Korean War when thousands of soldiers suffered from an acute renal syndrome, Hemorrhagic Fever with Renal Syndrome/HFRS)
- This occured near the Hantaan River, for which the virus was named.
- New World Hantaviruses have been implicated as the cause of Hantavirus Pulmonary Syndrome (HPS)
- These hantaviruses were first identified as the agent involved in a deadly outbreak in 1993 in the Southwest United States
- Family: Bunyaviridae
- Genus: Hantavirus (type species: Hantaan virus)
- Species: Sin Nombre Virus (Spanish: “No name virus”)
- This is one of several “New World Hantaviruses” that cause Hantavirus Pulmonary Syndrome
- Unlike HFRS, which has a mortality rate of 1-15%, SNV has a death rate of over 50%.
Species of Hantavirus
- At present there are 22 species of hantavirus, eg.
- Hantaan, the type species, cause of HFRS
- Sin Nombre, a cause of HPS
- It's unknown whether these constitute species due to lack of evidence:
- Up to 7% sequence difference
- However, reassortment viruses have been produced in a lab environment.
- In 1993, an unidentified pulmonary disease took place in the “Four Corners” region of the Southwest United States (Arizona, New Mexico, Colorado, Utah)
- An adult male of good health came down with acute respiratory problems and died shortly after being transported to the hospital.
- Just days before, it was found that the man's fiancee died of similar causes.
1993 Outbreak (2)
- Lab tests could not identify what the virus was
- Many new cases were being reported at the same time.
- Serologic tests eventually identified the disease as a new type of Hantavirus
- Since existing Hantaviruses could be spread by rodent populations, rodents were trapped near the locations cases were reported.
- Out of a total of 53 cases, the virus caused 32 deaths.
1993 Outbreak (3)
Sin Nombre Virus
- Sin Nombre was the first of the “New World” hantaviruses to be discovered during the 1993 outbreak.
- Today, there are 9 known strains:
- Blue River (Indiana and Oklahoma)
- Convict Creek (three strains)
- NMH10 (three strains)
New World Hantaviruses
- Hantaviruses gain entry via RME:
- β3 integrins on endothelial cells
- Mostly in the lung where they cause pulmonary edema
- Also in macrophages
- Specifics such as viral protein residues involved have not yet been elucidated
- β3 integrins are being considered as a possible drug target
Sin Nombre TEM
- Hantaviruses specifically have a negative-sense ssRNA delivered in three segments:
- small (S)
- middle (M)
- large (L)
- These segments circularize due to complimentary 5' and 3' base pairing.
- Hantaviruses are simple: They only encode four genes!
- Nucleocapsid protein (N) is encoded in the S segment and forms the helical nucleocapsid
- Transmembrane glycoproteins G1 and G2 (or Gn and Gc) are cleaved from a polycistron product encoded by M
- RNA-dependent RNA Polymerase (L) is encoded in the L segment.
Proteins: Coiled-coil Domain of SNV
Proteins: G1 Tail — Dual zinc fingers
Capsid and Envelope
- All bunyaviridae have a helical nucleocapsid
- Some evidence suggests viral envelope derives from the PM.
- Most members of the family gain envelope from the Golgi.
- Conflicting evidence for both.
- Forms spherical pleomorphic particles once bud
- These range in size from 70 to 210 nm
- Evidence suggests range in size and shape may be due to excess genome copy number
Bunyaviridae Virion Overview
- Most bunyaviridae spread through arthropods, eg. mosquitos.
- Hantaviruses utilize rodents as their reservoir
- Sin Nombre in particular spreads via:
- deer mice (predominantly)
- cotton rats
- rice rats
- white-footed mice
- Human infection is predominantly caused by inhalation of aerosolized urine, feces, or saliva.
- Bites or scratches are rare
- This is a zoonotic disease: only one case of human-to-human spread has been documented for HPS.
- Virus is subject to damage from UV light
- Indoor spaces with poor ventilation that allow rodent access can be dangerous.
- Many cases involve cleaning garages or attics.
- Incubation time not known at present
- Estimated to be between one and five weeks
- Initial symptoms include
- High fever
- Muscle ache
- Half of HPS cases also report:
- Abdominal pain
- Within four to ten days after the onset of initial symptoms:
- Coughing, shortness of breath.
- Lungs become flooded with fluids
- Machine ventilation usually becomes necessary
- Half of the cases result in death resulting from drowning in one's own body fluids
- Most cases involve white males in rural areas
- This may be due to occupational reasons rather than immunological ones.
- Children under 15 seem to contract a milder form of HPS
- HLA (MHC) typing suggests that those with the B35 allele are at particularly high risk of the severe form of the disease.
- Serologic tests:
- ELISA against IgM
- A neutralizing plaque assay and hemagglutination inhibition assay have been described in the literature, but are not available commercially.
- All research on hantaviruses are carried out under extreme care:
- BSL-3 facilities for cell cultures
- BSL-4 facilities for rodent work
- Isolation from human hosts has not yet been possible
- Microscopy of rodents reveals presence of inclusion bodies
- Without access to serum, retroactive analysis (perhaps of cadavers) can be done with immunohistochemistry
- These studies reveal cases of Sin Nombre virus infections occurring as early as the 1950's.
- (No histology course = sad)
Be careful when cleaning the basement!