Lymphocytic choriomeninigitis virus (LCMV)

Characteristics
Morphology	A member of the family Arenaviridae, genus Arenavirus, Lymphocytic choriomeninigitis virus (LCMV) is an enveloped, round, oval, or pleomorphic virion, measuring roughly 110 nm to 130 nm in diameter with a bipartite single-stranded RNA genome. The virion interior contains granules resembling grains of sand, which are characteristic of the family Arenaviridae, while the surface has hollow golf-club shaped projections. Initially isolated in 1933, infections have been reported in Europe, the Americas, Australia, and Japan, and may occur wherever infected rodent hosts of the virus are found.
Growth Conditions	Fibroblast or epithelial cell lines (37°C, 5% C02)

Characteristics

Morphology

A member of the family Arenaviridae, genus Arenavirus, Lymphocytic choriomeninigitis virus (LCMV) is an enveloped, round, oval, or pleomorphic virion, measuring roughly 110 nm to 130 nm in diameter with a bipartite single-stranded RNA genome. The virion interior contains granules resembling grains of sand, which are characteristic of the family Arenaviridae, while the surface has hollow golf-club shaped projections. Initially isolated in 1933, infections have been reported in Europe, the Americas, Australia, and Japan, and may occur wherever infected rodent hosts of the virus are found.

Growth
Conditions

Fibroblast or epithelial cell lines (37°C, 5% C02)

Health Hazards
Host Range	Humans, mice, hamsters, guinea pigs, rats, monkeys, dogs, rabbits, and chickens
Modes of Transmission	Infections can occur after exposure to fresh urine, droppings, saliva, or nesting materials from infected rodents. Transmission may also occur when these materials are directly introduced into broken skin, the nose, the eyes, or the mouth, or presumably, via the bite of an infected rodent. Person-to-person transmission has not been reported, with the exception of vertical transmission from infected mother to fetus, and rarely, through organ transplantation.
Signs and Symptoms	Most commonly recognized as causing neurological disease, as its name implies, though the number of acquired LCMV cases is underestimated since most cases are mild or asymptomatic and such individuals rarely seek medical attention. During the initial phase, which may last as long as a week, typically begins with any or all of the following symptoms: fever, malaise, lack of appetite, muscle aches, headache, nausea, and vomiting. Other symptoms appearing less frequently include sore throat, cough, joint pain, chest pain, testicular pain, and parotid (salivary gland) pain. A second phase of illness may occur afterwards and involve meningitis, encephalitis, or meningoencephalitis. LCMV does not have a high mortality rate. In general, mortality is less than 1%.
Infectious Dose	Unknown
Incubation Period	Approximately 8 to 13 days and 15 to 21 days before any meningeal symptoms appear

Medical Precautions/Treatment
Prophylaxis	None publically available
Vaccines	None publically available
Treatment	Treatment of secondary phases requires hospitalization and supportive treatment based on severity. Anti-inflammatory drugs, such as corticosteroids, may be considered under specific circumstances.
Surveillance	Monitor for symptoms. Diagnosis is confirmed by serology, ELISA, RT-PCR, Western blot, immunoassays, and viral culture from blood or cerebrospinal fluid.
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/ABSL-2	Risk Group 3 classification is applied to LCMV. BSL-2 practices, containment equipment, and facilities are suitable for activities utilizing known or potentially infectious body fluids and for cell culture passage of laboratory-adapted strains. ABSL-2 practices, containment equipment, and facilities are suitable for studies in adult mice with mouse brain-passaged strains requiring BSL-2 containment.
BSL-3/ABSL-3	BSL-3 is also required for activities with high potential for aerosol production, work with production quantities or high concentrations of infectious materials, and for manipulation of infected transplantable tumors, field isolates, and clinical materials from human cases. Strains of LCMV that are shown to be lethal in non-human primates should be handled at BSL-3. Work with infected hamsters should be done at ABSL-3.

Containment

BSL-2/ABSL-2

Risk Group 3 classification is applied to LCMV. BSL-2 practices, containment equipment, and facilities are suitable for activities utilizing known or potentially infectious body fluids and for cell culture passage of laboratory-adapted strains. ABSL-2 practices, containment equipment, and facilities are suitable for studies in adult mice with mouse brain-passaged strains requiring BSL-2 containment.

BSL-3/ABSL-3

BSL-3 is also required for activities with high potential for aerosol production, work with production quantities or high concentrations of infectious materials, and for manipulation of infected transplantable tumors, field isolates, and clinical materials from human cases. Strains of LCMV that are shown to be lethal in non-human primates should be handled at BSL-3. Work with infected hamsters should be done at ABSL-3.

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. LCMV exposure via aerosol transmission is a possibility, 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 (bleach, povidone-iodine, and chlorhexidine), 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.

LCMV exposure via aerosol transmission is a possibility, 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 (bleach, povidone-iodine, and chlorhexidine), 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 10% bleach, 70% ethanol, and other common cleaners.
Inactivation	Exposure to ultraviolet light and heat (55°C for at least 20 minutes) will inactivate the virus
Survival Outside Host	Unless it is preserved at -80°C, LCMV is quickly inactivated outside its host. LCMV will retain its infectivity for at least 206 days if stored in 50% glycerine and 0.85% saline at 4-10°C.

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 LCMV. 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 and when working at higher containment levels, such as solid-front gowns with tight fitting wrists, gloves, and respiratory protection. Eye protection must be used where there is a known or potential risk of exposure to splashes

References
CDC (https://www.cdc.gov/vhf/lcm/index.html) BMBL 6th Edition (https://www.cdc.gov/labs/BMBL.html) Canadian PHAC (https://www.canada.ca/en/public-health/services/laboratory-biosafety-bi…) ABSA (https://my.absa.org/riskgroups)