Table 1.

Summary of the advantages and disadvantages of viral-vectored receptor expression for developing mouse models of viral infection.

Advantages	Limitations
Rapid model development: simply need to synthesize and clone the receptor gene and produce viral vector.	Requires a priori knowledge of the receptor molecule(s) that the virus uses to enter cells.
Ability to use any strain of commercially available laboratory mice, including aged mice and transgenic mice, e.g., IFNR−/−, STAT1−/−, Sting−/−, which can be purchased quickly and easily in large numbers if necessary. There is also the potential to use other animal species, including Syrian hamsters, ferrets, etc. However, the use of other species may be contraindicated and/or pose additional challenges beyond what is presented for mice, including the need for much larger doses of the vector and the possibility of an immune response to the transgene, leading to rapid clearance of vector-transduced cells.	This approach will not be able to overcome intracellular blocks to virus replication unless there are readily available transgenic mice that already have this block to virus replication knocked out. However, this would also be a limitation in transgenic models as well.
Ability to perform sophisticated immunological studies due to the plethora of reagents readily available for studies involving mice.	Targeting specific organs, such as the lungs, liver, or brain, is better suited for vectored receptor expression strategies compared with those that necessitate widespread or blood cell receptor expression.
Can use authentic/natural virus isolates without having to go through the lengthy process of mouse or other species adaptation.	Potential for mouse-to-mouse variations in transgene expression, as well as variability in transgene expression between tissues.
Use of authentic virus in challenge studies allows for more accurate testing of antibody therapies that target the receptor-binding domain (RBD) of the virus	Mild bronchial inflammation is associated with AdV delivery.
Ability to express more than one protein involved in the virus life cycle, for example, hACE2 and TMPRSS2 in the case of SARS-CoV-2.	The potential for mouse-to-mouse variation in transduction efficiency could lead to transgene expression differences.
Ability to administer the vector via any route of administration and with inducible promoters for controlled receptor expression.
Possible to evaluate co-infection in a mouse model by using vectored delivery of two virus receptors, e.g., hACE2 and hDPP4 to study SARS-CoV-2 and MERS-CoV co-infection.