Table 3.

In vivo models for HDV infection.

Model	Entry	HBV Co-Infection	Immuno-Competent	Pros	Cons	Ref.
Chimpanzee	+	+	+	Immunocompetent infection model	Ethical considerations	[54,55,56]
Woodchuck	+/-	+ 1	+	Immunocompetent infection model	Relies on WHV rather than HBV envelope	[57,59,69]
HDV/HDAg-transgenic mice	-	-	+	Stable mouse lines; tissue-specific expression can be analyzed	No virus infection/spread	[60,61]
Hydrodynamic injection	-	-	+	Fast and easy way to deliver nucleic acids to the liver	No virus infection/spread; harmful to the animal	[62,63]
AAV-HDV transduction	-	-	+	Allows studies of host virus interactions in vivo	No authentic infection system	[70]
Liver-chimeric mice	+	+	-	Authentic HBV/HDV infection; allows for long-term infections	No adaptive immunity; very sophisticated model	[66,67]
hNTCP mice	+	-	+	Immunocompetent transgenic infection system	Low infection rates, transient infection	[64,65]
Macaque/pig hNTCP-transduced	+	+	+	Immunocompetent models allowing authentic infection	Only in vitro data available so far; sophisticated animal models	[15,71]

¹ Co-infection only with WHV, not with HBV. WHV: Woodchuck Hepatitis Virus.