RABBITS AS A MODEL FOR HIV INFECTION
The human immunodeficiency virus type 1 (HIV-1) has become one of the most devastating pandemics in recorded history. Currently over 37.7 million people are living with HIV-1 and about 680.000 suffered AIDS-related deaths in 2020 (unaids.org). Until now, no protective vaccine against HIV is in sight and currently available pharmacotherapies can only partly control, but not cure infection. The thus imperative development of alternative strategies against HIV has been hampered by the lack of small animal models that are highly permissive to infection.
An immunocompetent, permissive small animal model would be valuable for the study of HIV-1 pathogenesis and for the testing of drug and vaccine candidates. One approach are the widely used HIV xenotransplant models. Another alternative is the identification and surmounting of species-specific barriers that HIV encounters along its replication cycle in cells from small animals. These species-specific barriers are either due to missing/non-functional cellular co-factors, which HIV-1 hijacks at different steps of its life cycle for efficient replication, or due to the presence of restriction factors, which block HIV-1 replication at distinct steps and cannot be counteracted by accessory HIV proteins.
Therefore, we, the VIIRAL lab, want to understand how innate immunity factors work in a species-specific context - identifying thereby specific signaling pathways and motifs, which are involved to elucidate the mode of action of the immunity factors, and how the virus antagonizes them. Building on our work on innate immunity factors (Tervo et al., 2008; Tervo et al., 2011; Baldauf et al., 2012; Baldauf et al., 2017) as well as our observation that rabbits as a species display fewer blocks to HIV-1 replication than mice or rats (Tervo and Keppler, 2010), we want to develop a fully permissive transgenic rabbit model to find novel strategies for the prevention or treatment of HIV/AIDS.
Summary of the efficiency of steps in the HIV-1 replication in primary cells of human, rat, mouse and rabbit origin. Schematic representation of consecutive steps in the HIV-1 replication cycle and the ability of primary cells (T = T-cells; M = macrophages) from the respective species to support these steps (√ = efficient; x = inefficient or completely blocked). Yellow boxes indicate blocks in the rabbit species (Tervo and Keppler, 2010).
Key publications on this topic
Schelle L, Côrte-Real IV, Esteves PJ, Abrantes J, Baldauf HM. (2022)
Baldauf HM, Weingartner S, Hofmann K, Mitteregger-Kretzschmar G, Popper B, Bönisch MP, Keppler OT. (2021)
Pereira et al.
Journal: The Journal of General Virology
Cano-Ortiz L Gu Q, de Sousa-Pereira P, Baldauf HM, et al. (2022)
Matzek D, Baldauf HM, Schieweck R, Popper B. (2021)
Tervo and Keppler
Journal: Journal of Virology
Photo by Maik Richter