Table 2.

In vivo studies of the role of NF-κB signaling on MHV68 pathogenesis.

Gene	Knockout	Immune defects	Route/Dose	Impact on pathogenesis	Changes in host response	Reference
LTα	Germline	No lymph nodes	INa/2 × 105,b	↓ Clearance from lung	↑ Lung inflammation	Lee et al., 2000
				↑ Latency	↓ CD8+ T cell activation
CD40	Germline	No germinal center formation	IN/1 × 103	↑ Reactivation		Willer and Speck, 2005
				↑ Infection of naïve B cell
				Recrudescence in lungs
CD40	Mixed BM chimera		IN/4 × 102	Equal latency establishment Loss of latency in CD40-/- subset	Exclusion of CD40-/- B cells from germinal center	Kim et al., 2003
BAFFR	Germline	↓ Mature B cells Impaired Abc production	IN/1 × 104	↓ Latency at 30 dpid	↓ Germinal centers	Frederico et al., 2014b
					↓ MHV68-specific Ab
			IPe/1 × 105	↑ Viral titer at 3 dpi,
				↓ Infection from 8–30 dpi
TLR2/9	Germline		IN/5 × 104	↑ Viral load at 3 dpi		Sun et al., 2015
TLR3	Germline		IN/1 × 103	None		Gargano et al., 2008
TLR7	Germline		IP/1 × 105	None		Haas et al., 2014
TLR9	Germline		IP/1 × 105	↑ Reactivation
MyD88	Germline	↓ B cell activation	IN/1 × 103	↓ Latency in spleen at 16 dpi	↓ B cell activation	Gargano et al., 2008
				No difference in latency at 90 dpi	↓ Germinal centers
					↓ Class switching
					Delayed ab production
			IP/1 × 103	↑ Reactivation in PECs
				↓ Reactivation in spleen
	Mixed BM f Chimera		IN/1 × 103	↓ Latency	↓ MyD88-/- germinal center entry
IkBaM	Viral Transgene		IN/1 × 103	↓ Latency establishment		Krug et al., 2007
				↓ Infected lung B cells
			IP/1 × 103	↓ Viral titer
				↓ Latency
p50	Germline	↓ B cell proliferation	IN/1 × 102	↑ Viral titers in lung	↓ Antibody production	Krug et al., 2009
		↓ Ab levels		↓ Latency at 16 dpi	↓ Vβ4+ T cell
		↓ Germinal centers		↑ Latency over time
				Recrudescence in lungs
	Mixed BM chimera	None	IN/1 × 102	Normal lung titers	↓ p50-/- germinal center B cell
				↓ Latency in p50-/- B cells
				Recrudescence in lungs

^aIN, intranasal infection under light anesthesia.

^bDose described as PFU per animal.

^cAb, antibody.

^ddpi, days post infection.

^eIP, intraperitoneal infection.

^fBM, bone marrow.