Hantavirus

Characteristics
Morphology	A zoonotic negative-sense (tripartite single-stranded) RNA viruses belonging to the genus Hantavirus within the family Bunyaviridae. They are enveloped viruses about 100 nm in diameter, enclosed within a spherical capsid
Growth Conditions	Various cell lines can be infected (ex. Vero, Huh7)

Health Hazards
Host Range	Field rodents (mice, rats, voles, lemmings) and mammals including humans.
Modes of Transmission	Respiratory and fecal-oral routes. AdV can also spread through contaminated fomites, ingestion, and inhalation of aerosolized droplets. Transmission occurs mainly by inhalation of aerosolized droplets of urine, saliva, or respiratory secretions from infected rodents or of aerosolized particles of feces, dust, or other organic matter carrying the infectious virus. They may also be transmitted by rodent bites ingestion of contaminated food or water, and direct contact of cutaneous injuries or mucous membranes with the infectious virus.
Signs and Symptoms	Hemorrhagic fever with renal syndrome (HFRS): Caused by the Puumala, Seoul or Seoul-like viral species. Initial symptoms begin suddenly and include intense headaches, back and abdominal pain, fever, chills, nausea, and blurred vision. After 3-6 days, hemorrhagic manifestation occurs and is followed by hypotension, proteinuria, and shock. The case fatality rate is 5 to 15% Hantavirus pulmonary syndrome (HPS): Caused by the Sin Nombre or Andes viral species. Disease begins with fever, chills, myalgia, and hypotension. There may also be headaches, dizziness, chills, and abdominal problems, such as nausea, vomiting, diarrhea, and abdominal pain. Death then occurs in approximately 35-38% of US cases due to pulmonary edema and shock.
Infectious Dose	Unknown
Incubation Period	2 to 4 weeks (range from few days to 2 months) for HFRS; and 14-17 days for HPS

Medical Precautions/Treatment
Prophylaxis	None publically available
Vaccines	None publically available
Treatment	Antivirals can improve outcomes, but most treatment is supportive. Care includes careful management of the patient’s fluid (hydration) and electrolyte (e.g., sodium, potassium, chloride) levels, maintenance of correct oxygen and blood pressure levels, and appropriate treatment of any secondary infections.
Surveillance	Monitor for symptoms. Diagnosis is based mainly on serological tests to detect Hantavirus specific antibodies against the N protein or glycoproteins. RT-PCR can also be used
GWU Requirements	Report all incidents to the Office of Risk Management as well as the Office of Research Safety (ORS) IMMEDIATELY FOLLOWING THE OCCURRENCE.

Containment
BSL-2	Risk Group 3 classification is applied to hantavirus. BSL-2 practices, containment equipment, and facilities are recommended for laboratory handling of sera from persons potentially infected with hantaviruses. All procedures that may produce aerosols, or involve high concentrations or large volumes should be conducted in a biological safety cabinet (BSC).
BSL-2+	Serum or tissue samples from potentially infected sources should be handled at BSL-2 using BSL-3 practices, containment equipment, and procedures.
BSL-3	Cell-culture virus propagation and purification should be carried out in a BSL-3 facility using BSL-3 practices, containment equipment, and procedures.
ABSL-2	Experimentally infected rodent species known not to excrete the virus can be housed in ABSL-2 facilities using ABSL-2 practices and procedures.
ABSL-4	All work involving inoculation of virus-containing material into rodent species permissive for chronic infection should be conducted at ABSL-4.

Spill Procedures
Small Spills (<1 liter)	If the spill occurred inside a biological safety cabinet, close the sash and allow the cabinet to operate for 15 minutes before continuing with the spill cleanup. Hantavirus can be transmitted via aerosols, so caution should still be taken during a spill outside of a BSC. Leave the room immediately and allow the aerosols to dissipate for 15 minutes. Notify others working in the lab. Don appropriate PPE. Cover area of the spill with paper towels or any absorbent material and apply an EPA registered disinfectant effective against enveloped viruses (alcohols, bleach, and quaternary ammonium compounds), working from the perimeter towards the center. Allow 30 minutes of contact time before disposal and cleanup of spill materials.
Large Spills	Alert lab personnel in the laboratory to the spill and keep people out of the area to prevent spread of the contamination. Check if you have been contaminated or if any of your PPE has been breached. If so follow exposure procedures. Remove any contaminated clothing and place it the biohazard waste. Wash your hands and post a sign on the door. Notify your supervisor of the incident and call ORS (4-8258) for assistance. If the situation involves an imminently life-threatening injury or has catastrophic potential, call 911.

Spill Procedures

Small Spills (<1 liter)

If the spill occurred inside a biological safety cabinet, close the sash and allow the cabinet to operate for 15 minutes before continuing with the spill cleanup.

Hantavirus can be transmitted via aerosols, so caution should still be taken during a spill outside of a BSC. Leave the room immediately and allow the aerosols to dissipate for 15 minutes. Notify others working in the lab. Don appropriate PPE. Cover area of the spill with paper towels or any absorbent material and apply an EPA registered disinfectant effective against enveloped viruses (alcohols, bleach, and quaternary ammonium compounds), working from the perimeter towards the center. Allow 30 minutes of contact time before disposal and cleanup of spill materials.

Large Spills

Alert lab personnel in the laboratory to the spill and keep people out of the area to prevent spread of the contamination. Check if you have been contaminated or if any of your PPE has been breached. If so follow exposure procedures. Remove any contaminated clothing and place it the biohazard waste. Wash your hands and post a sign on the door. Notify your supervisor of the incident and call ORS (4-8258) for assistance. If the situation involves an imminently life-threatening injury or has catastrophic potential, call 911.

Exposure Procedures
Mucus Membrane	Flush eyes, mouth or nose for 15 minutes at eyewash station.
Other Exposure	Wash area with soap and water for 15 minutes.
Reporting	Report ALL injuries to the PI immediately and reported to the Office of Risk Management at [email protected] IMMEDIATELY FOLLOWING THE OCCURRENCE. Exposures that involve a bloodborne-pathogen or recombinant DNA also need to be reported to the Office of Research Safety at [email protected]. If the injury requires immediate medical attention, call GWPD at 202-994-6111 or call 911.
Medical Monitoring	Seek immediate medical evaluation, treatment, and post exposure follow-up at the Employee Health Office at GWU Hospital (900 23rd St., NW, Suite G-1090, Phone: 202-715-4275). Students should go to the Students Health Office at Marvin Center. After hours treatment can be received at the GWU hospital emergency room.

Stability
Disinfection	Susceptible to 70% Ethanol, 10% bleach, and 2% glutaraldehyde. Quaternary ammonium compounds can be used as well
Inactivation	Inactivated by heat (15 min at 56ºC for viruses in cell culture medium, 2 hours at 56oC for dried viruses), and through exposure to acidic conditions (pH ≤ 5)
Survival Outside Host	Dried cell cultures (2 days), salt solutions with 1% bovine albumin at -60°C (5 years).

Personal Protective Equipment (PPE)
Minimum PPE Requirements	At minimum, personnel are required to don gloves, closed toed shoes, lab coat, and appropriate face and eye protection prior to working with hantavirus. Additional PPE may be required depending on lab specific SOPs.
Additional Precautions	Additional protection may be worn over laboratory clothing when infectious materials are directly handled, such as solid-front gowns with tight fitting wrists, gloves, and respiratory protection.

References
CDC (https://www.cdc.gov/hantavirus/) BMBL 6th Edition (https://www.cdc.gov/labs/BMBL.html) Hantavirus Infection Is Inhibited by Griffithsin in Cell Culture (https://www.frontiersin.org/articles/10.3389/fcimb.2020.561502/full) Canadian PHAC (https://www.canada.ca/en/public-health/services/laboratory-biosafety-bi…)