Important: Changes to the classification of the ZKBS – affecting Mammalian 1 orthobornavirus (BoDV), pestiviruses and genetic engineering work with recombinant influenza A viruses (FLUAV)

1. The Mammalian 1 orthobornavirus

Background: The virus formerly known as Borna disease virus (BoDV) is the causative agent of Borna disease. A wide variety of animal species can be infected, including horses, sheep, dogs, and cats, as well as humans, but the highest incidence of infection is seen in horses and sheep. The virus is known to initially replicate in the neurons at the point of entry before traveling along the nerve pathways to the brain. Neither direct transmission from farm animal to farm animal nor direct transmission from farm animals to humans is known to date. However, transmission of the virus by mice (vertical transmission to offspring) and rats (horizontal transmission through urine) has been experimentally confirmed. Several fatal cases in humans have also attracted attention. Firstly, in October 2018, several cases were reported in which two recipients of organ donations from the same donor developed fatal BoDV, and another recipient became blind. Furthermore, other fatal cases have been reported, but no information on virus transmission is available. Until 1992, various inactivated and live vaccines against BoDV were available in Germany. However, since their effectiveness could never be proven, their approval expired in 1992. Since then, cases of Borna disease have not increased significantly.

Classification: As a donor and recipient organism for genetic engineering work, BoDV is currently assigned to Risk Group 2. This classification also applies to the "Technical Rules for Biological Agents (TRBA) 462: Classification of Viruses." The AGCT will soon offer a modular course that addresses, among other things, the TRBA and thus also the background of virus classification. Further information and registration can be found here! The ZKBS maintains the classification in Risk Group 2 and justifies this as follows:

Reason: Mammalian 1 orthobornavirus can cause severe, even fatal, encephalitis in humans. Furthermore, the route of transmission to humans is not yet known. This makes the virus dangerous to humans. However, since no cases of infection in laboratories have been reported to date, it can be assumed that the current Level 2 safety precautions sufficiently limit the risk of infection. For this reason, the classification will not be changed.

Further information: The ZKBS notes that infected mice and rats must be kept in individually ventilated cages (IVCs) and that cage changing stations must be used to move the animals in order to prevent airborne transmission of the virus.

2. Pestiviruses

The ZKBS has also reclassified a number of newly discovered and, in some cases, provisional species of the genus Pestivirus. Some of the species were only identified in recent years, prompting the need for reclassification. Below is the updated classification of pestiviruses by risk group:

 Risk group 1:

• Pestivirus J (Norwegian rat pestivirus, NrPV)
• Bat pestivirus 1 (provisional species)
• Bat pestivirus 2 (provisional species)
• Rodent pestivirus 1 (provisional species)
• Rodent pestivirus 2 (provisional species)
• Rodent pestivirus 3 (provisional species)
• Rodent pestivirus 4 (provisional species) The ZKBS justifies this decision by stating that the above-mentioned species cannot yet be linked to any disease. Furthermore, according to current research, the viruses do not affect even-toed ungulates, meaning they have only a minor economic impact. Risk group 2:
• Pestivirus A (Bovine viral diarrhea virus 1, BVDV-1)
• Pestivirus B (Bovine viral diarrhea virus 2, BVDV-2)
• Pestivirus C (Classical swine fever virus, CSFV)
• Pestivirus D (border disease virus, BDV)
• Pestivirus E (pronghorn antelope virus, PHV)
• Pestivirus F (Bungowannah virus)
• Pestivirus G (giraffe pestivirus)
• Pestivirus H (HoBi-like viruses; atypical ruminant pestivirus; BVDV-3)
• Pestivirus I (Aydin-like pestivirus)
• Pestivirus K (atypical porcine pestivirus, APPV)
• Linda Virus (lateral-shaking inducing neurodegenerative agent virus, LV) The ZKBS justifies this classification by stating that it cannot currently be ruled out that the Pestivirus E species is pathogenic to animals. The other species assigned to risk group 2 have this same pathogenicity and can infect wild and farm animals, sometimes causing serious illness. Due to the danger they pose to farm animals, these viruses can also have significant economic consequences if they spread. Some of the classifications are precautionary recommendations that may be adjusted by the ZKBS if new research results become available. Should this be the case, the AGCT will inform you in its newsletter as usual.

3. Recombinant Influenza A Viruses (FLUAV) At its 219th meeting, the ZKBS also published an updated list of mutations that are significant for the risk assessment of genetic engineering work with recombinant influenza A viruses. The list of mutations provides an assessment aid for project leaders in the risk classification of their organisms and is continuously updated by the ZKBS. Such an update has now been published. The list specifies a statement published by the ZKBS in February 2018 on the risk assessment of genetic engineering work with recombinant influenza A virus mutants and reassortants. Project leaders working with influenza A viruses should check the updated list to see if there are any significant changes regarding the risk assessment of the types they are using.