Alongshan virus: Infectious substances pathogen safety data sheet

Section I – Infectious agent

Name

Alongshan virus

Agent type

Virus

Taxonomy

Family

Flaviviridae^{Footnote 1Footnote 2Footnote 3}

Genus

Unclassified

Species

Unclassified

Subspecies/strain/clonal isolate

Jingmenvirus group

Synonym or cross-reference

Prior to its naming, Alongshan virus (ALSV) was known as a novel virus that was associated with human febrile illness while also being found in animals^{Footnote 1Footnote 4}, or simply as a unclassified Jingmenvirus^{Footnote 1}.

Characteristics

Brief description

ALSV is a newly discovered pathogenic virus, and known to be a member of the unclassified Jingmenvirus (JMV) group^{Footnote 1} . ALSV is currently considered a tick-borne arbovirus^{Footnote 5}.

In contrast to other viruses classified under the family Flaviviridae, the genomes of the unclassified Jingmenviruses have segmented genomes^{Footnote 1} . ALSV genome is approximately 11 kb^{Footnote 3} and consists of four segments (S1-S4)^{Footnote 2} of positive-sense single-stranded RNA^{Footnote 1} . The four segments encode five structural proteins (VP1a, VP1b, VP2, VP3, and VP4) and two non-structural proteins (NSP1 and NSP2)^{Footnote 2} . ALSV virions are enveloped, spherical in shape, and approximately 40.5 nm in diameter^{Footnote 3Footnote 6}.

Properties

Similar to all viruses in the family Flaviviridae, ALSV is believed to enter the cell via endocytosis, exposing the particles to an acidic endosome that triggers the release of viral RNA into the cytosol^{Footnote 2}. The released RNA is then translated at the rough endoplasmic reticulum (ER) into a single polyprotein, which is cleaved into structural and non-structural proteins by viral and cellular proteases. The viral RNA molecules generated by the viral replicase complex are incorporated into viral particles which involve RNA encapsidation and budding into the lumen of the ER. The newly synthesized virus particles are transported to the cell surface, and released by exocytosis.

Section II – Hazard identification

Pathogenicity and toxicity

The clinical symptoms of ALSV infection are very similar to those reported in cases of infectious tick-borne encephalitis virus (TBEV)^{Footnote 3}. Reported signs of infection include headache, fever, fatigue, depression, coma, poor appetite, nausea, myalgia or arthralgia, rash or petechiae, cough/pharyngeal discomfort, vomiting, lymphadenopathy, abdominal pain or tenderness, chills, and diarrhea^{Footnote 3}. Laboratory testing showed that the most common abnormal findings in patients were elevated or decreased levels of lactate dehydrogenase and elevated levels of high-sensitivity C-reactive proteins. For long term infection, both muscle and liver injury have been reported. Additionally, imaging of the central nervous system indicating mild ischemic demyelination of the white matter of the brain has been reported.

Epidemiology

ALSV was first isolated from human case in April 2017^{Footnote 3}. The patient, a 42 year old female farmer from the town of Alongshan located in Inner Mongolia, China, presented with fever, headache, and a history of tick bites. From May to September 2017, a total of 86 ALSV cases were confirmed, and of these, 60 were from Inner Mongolia and 24 were from Heilongjiang (the location is unknown for 2 patients). Symptoms in these patients typically resolved after 6-8 days of treatment, and all patients had complete clinical recovery (no fatal outcomes nor permanent clinical complications). During 2018-2019, 30 cases of ALSV infection were reported in humans, with mild liver damage reported, and again, no fatal outcomes were reported^{Footnote 7}. In total, there have been 117 ALSV cases that have been reported in human patients in China^{Footnote 3Footnote 7} .

In 2019, 480 serum samples were collected from sheep and cattle from Inner Mongolia, China, with approximately 39% of sheep (95/240) and 33% of cattle (81/240) tested positive for ALSV^{Footnote 4} . Similarly, in 2024, 21 serum samples from reindeer were collected from Northeastern China, with only 1 reindeer having ALSV viremia, however, in the others, there were high prevalences of ALSV IgG (33.3%) and neutralizing antibodies (19.1%)^{Footnote 8}. There are no reports of disease symptoms in seropositive animals.

ALSV has also been identified in various species of ticks from Germany^{Footnote 9}, Finland^{Footnote 10}, Russia^{Footnote 6} (including Eastern Siberia)^{Footnote 11}, and Switzerland^{Footnote 1} .

Host range

Natural hosts

Natural hosts include humans^{Footnote 3}, cattle^{Footnote 4 Footnote 8} , sheep^{Footnote 4 Footnote 8 Footnote 9} , goats^{Footnote 8 Footnote 9} , horses, roe deer, and red deer.

Other hosts

Mice were experimentally infected^{Footnote 3}.

Infectious dose

Unknown.

Incubation period

The incubation period is between 3 to 7 days^{Footnote 3}.

Communicability

The preferred route of transmission for ALSV is via arthropod-mediated transmission, by the bite of a tick^{Footnote 3Footnote 5}. In experimental settings, intraperitoneal injection of ALSV has been shown to induce pathologic changes^{Footnote 3}.

The transmission cycle of ALSV occurs via indirect transmission between natural hosts and is maintained by tick vectors^{Footnote 9} . Natural hosts serve as blood meals for tick vectors, and subsequently, due to ALSV in the tick’s saliva, another natural host become infected.

Section III – Dissemination

Reservoir

Reindeer in China are suspected to be the primary reservoirs for ALSV^{Footnote 8} . However, based on natural prevalence, other candidates could include sheep^{Footnote 4} , cattle^{Footnote 4} , horses^{Footnote 9} , roe deer, and red deer.

Zoonosis

There is no reports of direct ALSV spreading between animals and humans.

Vectors

ALSV is spread via ticks. ALSV has been identified in Ixodes spp., such as I. Ricinus^{Footnote 1 Footnote 9 Footnote 10} and I. persulcatus^{Footnote 6Footnote 11} , as well in Dermacentor reticulatus^{Footnote 9}. Notably, RNA has also been detected in mosquitos in the Chinese province of Jilin, thus making them a likely vector for ALSV^{Footnote 3} .

Section IV – Stability and viability

Drug susceptibility/resistance

Efficacy has been shown for ribavirin, benzylpenicillin sodium, vinpocetine, and sulfotanshinone sodium for treating the ALSV infection^{Footnote 3} . 

Susceptibility to disinfectants

Compounds that can inactivate enveloped viruses include hydrochlorides such as sodium hypochlorite^{Footnote 12}, sodium dichloroisocyanurate, and hydrogen peroxide; phenolics such as chloroxylenol; alcohols such as ethanol/ethyl alcohol, propanol, and isopropyl alcohol; formaldehyde which includes both paraformaldehyde and formalin; glutaraldehyde; iodophors such as povidone iodine; quaternary ammonium compounds (QACs) such as chlorhexidine digluconate; and peracetic acid^{Footnote 12 Footnote 13}.

Members of the Jingmenvirus group can be inactivated by 3mM binary ethylenimime, 3-8% paraformaldehyde, 2% glutaradehyde, 1% hypochlorite, and 0.05% Tween 20^{Footnote 13} .

Physical inactivation

Viruses in the Flaviviridae family have been known to be physically inactivated by both UV radiation/light and heat. Viruses present in a serum or media can be inactivated by heating at 56°C for 30 minutes^{Footnote 14}.

Survival outside host

Unknown.

Section V – First aid/medical

Surveillance

ALSV can be detected using reverse transcriptase-polymerase chain reaction (RT-PCR)^{Footnote 3}, immunofluorescence, and microneutralization assays, along with RT-qPCR^{Footnote 5} and enzyme-linked immunosorbent assays (ELISA).

Note: The specific recommendations for surveillance in the laboratory should come from the medical surveillance program, which is based on a local risk assessment of the pathogens and activities being undertaken, as well as an overarching risk assessment of the biosafety program as a whole. More information on medical surveillance is available in the Canadian Biosafety Handbook .

First aid/treatment

There is no confirmed treatment for ALSV, however, documented treatment for humans includes a combination of ribavirin and benzylpenicillin sodium along with supportive care if necessary using drugs such as vinpocetine and sulfotanshinone for severe headaches^{Footnote 3}.

Note: The specific recommendations for first aid/treatment in the laboratory should come from the post-exposure response plan, which is developed as part of the medical surveillance program. More information on the post-exposure response plan can be found in the Canadian Biosafety Handbook.

Immunization

None.

Note: More information on the medical surveillance program can be found in the Canadian Biosafety Handbook, and by consulting the Canadian Immunization Guide.

Prophylaxis

None.

Note: More information on prophylaxis as part of the medical surveillance program can be found in the Canadian Biosafety Handbook.

Section VI – Laboratory hazard

Laboratory-acquired infections

None.

Note: Please consult the Canadian Biosafety Standard and Canadian Biosafety Handbook for additional details on requirements for reporting exposure incidents.

Sources/specimens

ALSV can be found in blood (including serum) samples^{Footnote 3 Footnote 4 Footnote 8} , and tick saliva^{Footnote 9} .

Primary hazards

Autoinoculation with the infectious material as well as bites from infected ticks are the primary hazards associated with ALSV^{Footnote 3}.

Special hazards

Work with experimentally or naturally infected ticks may present a special hazard.

Section VII – Exposure controls/personal protection

Risk group classification

ALSV is a Risk Group 3 Human Pathogen and a Risk Group 2 Animal Pathogen^{Footnote 15}.

Containment requirements

Containment Level 3 facilities, equipment, and operational practices outlined in the Canadian Biosafety Standard for work involving infectious or potentially infectious materials, animals, or cultures.

Protective clothing

The applicable Containment Level 3 requirements for personal protective equipment and clothing outlined in the Canadian Biosafety Standard are to be followed. At minimum, use of full body coverage dedicated protective clothing, dedicated protective footwear and/or additional protective footwear, gloves when handling infectious materials or animals, face protection when there is a known or potential risk of exposure to splashes or flying objects, respirators when there is a risk of exposure to infectious aerosols, and an additional layer of protective clothing prior to work with infectious materials or animals.

Note: A local risk assessment will identify the appropriate hand, foot, head, body, eye/face, and respiratory protection, and the personal protective equipment requirements for the containment zone must be documented.  

Other precautions

All activities involving open vessels of pathogens are to be performed in a certified biological safety cabinet (BSC) or other appropriate primary containment device. Centrifugation of regulated materials to be carried out in sealed safety cups or rotors that are unloaded in a BSC or other primary containment device using a mechanism that prevents their release. The use of needles, syringes, and other sharp objects are to be strictly limited. Additional precautions must be considered with work involving animals or large scale activities.

Proper precautions should be considered when working with infected arthropods. This might include implementing a program to prevent escapes and monitor any escaped arthropods, as well as using suitable personal protective equipment (PPE), among other measures^{Footnote 16Footnote 17}.

Section VIII – Handling and storage

Spills

Allow aerosols to settle. Wearing personal protective equipment, gently cover the spill with absorbent paper towel and apply suitable disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time before clean up (Canadian Biosafety Handbook).

Disposal

Regulated materials, as well as all items and waste, to be decontaminated at the containment barrier prior to removal from the containment zone, animal room, animal cubicle, or post mortem room. This can be achieved by using decontamination technologies and processes that have been demonstrated to be effective against the infectious material, such as chemical disinfectants, autoclaving, irradiation, incineration, an effluent treatment system, or gaseous decontamination (Canadian Biosafety Handbook ).

Storage

The applicable Containment Level 3 requirements for storage outlined in the Canadian Biosafety Standard are to be followed. Primary containers of regulated materials removed from the containment zone to be stored in a labelled, leak-proof, impact-resistant secondary container, and kept either in locked storage equipment or within an area with limited access.

An inventory of RG3 in long-term storage, to be maintained and to include:

• specific identification of the regulated materials
• a mechanism that allows for the detection of a missing or stolen sample in a timely manner

Section IX – Regulatory and other information

Canadian regulatory information

Controlled activities with ALSV require a Pathogen and Toxin licence issued by the Public Health Agency of Canada (PHAC). ALSV is also a terrestrial animal pathogen in Canada; therefore, its importation requires an import permit under the authority of the Health of Animals Regulations (HAR). The PHAC issues a Pathogen and Toxin Licence which includes a Human Pathogen and Toxin Licence and an HAR importation permit.

The following is a non-exhaustive list of applicable designations, regulations, or legislations:

• Human Pathogens and Toxins Act and Human Pathogens and Toxins Regulations
• Health of Animals Act and Health of Animals Regulations

Last file update

July, 2024

Prepared by

Centre for Biosecurity, Public Health Agency of Canada.

Disclaimer

The scientific information, opinions, and recommendations contained in this Pathogen Safety Data Sheet have been developed based on or compiled from trusted sources available at the time of publication. Newly discovered hazards are frequent and this information may not be completely up to date. The Government of Canada accepts no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information.

Persons in Canada are responsible for complying with the relevant laws, including regulations, directives and standards applicable to the import, transport, and use of pathogens and toxins in Canada set by relevant regulatory authorities, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment and Climate Change Canada, and Transport Canada. The risk classification and related regulatory requirements referenced in this Pathogen Safety Data Sheet, such as those found in the Canadian Biosafety Standard, may be incomplete and are specific to the Canadian context. Other jurisdictions will have their own requirements.

Copyright © Public Health Agency of Canada, 2024, Canada         

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