All-trans retinoic acid increases the pathogenicity of the H9N2 influenza virus in mice

Niu, Xiaofei; Wang, Hongyan; Zhao, Lihong; Lian, Pengjing; Bai, Yu; Li, Jingyun; Qiao, Jian

doi:10.1186/s12985-022-01809-y

Virology Journal

Table 2 Effects of different doses of ATRA and H9N2 virus on food intake in mice

From: All-trans retinoic acid increases the pathogenicity of the H9N2 influenza virus in mice

Clinical application of ATRA	Groups	Dosage of ATRA (mg/kg)	Time post-infection (days)
Clinical application of ATRA	Groups	Dosage of ATRA (mg/kg)	3	4	5	6	7	8	9	19
	Blank^a	0	113.1 ± 4.8	112.7 ± 4.7	110.0 ± 4.0	92.0 ± 5.2	96.7 ± 4.7	112.0 ± 5.6	124.0 ± 7.2	120.0 ± 5.9
Low therapeutic dose	ATRA1^b	1	110.7 ± 5.9	109.5 ± 6.3	105.1 ± 6.1	87.4 ± 7.3	89.7 ± 7.6	98.8 ± 9.6	119.0 ± 4.4	122.8 ± 5.2
Medium therapeutic dose	ATRA2^c	5	117.6 ± 6.3	114.3 ± 5.5	105.3 ± 6.1	91.8 ± 5.1	88.2 ± 5.6	100.4 ± 7.2	122.4 ± 8.6	119.9 ± 6.9
	ATRA3^d	10	115.1 ± 5.6	112.3 ± 6.2	102.3 ± 9.1	90.5 ± 10.7	86.7 ± 8.9	100.4 ± 8.9	107.2 ± 7.9	109.9 ± 7.9
High therapeutic dose	ATRA4^e	20	86.1 ± 9.4^∆∆	80.3 ± 13.3^∆	79.4 ± 13.8	65.3 ± 16.9	61.1 ± 16.2^∆∆	63.9 ± 15.3^∆∆	78.3 ± 12.2^∆∆	87.9 ± 7.9^∆∆
Toxic dose	ATRA5^f	40	68.3 ± 6.0^∆∆	43.0 ± 10.9^∆∆	35.1 ± 12.4^∆∆	17.7 ± 7.4^∆∆	15.9 ± 7.6^∆∆	15.9 ± 6.9^∆∆	22.1 ± 7.8^∆∆	—
	ATRA6^g	60	54.6 ± 6.9^∆∆	31.2 ± 7.3^∆∆	24.1 ± 7.4^∆∆	25.5 ± 7.0^∆∆	18.1 ± 5.5^∆∆	13.4 ± 5.0^∆∆	19.5 ± 5.7^∆∆	—
	ATRA7^h	80	39.3 ± 7.1^∆∆	13.2 ± 4.5^∆∆	17.6 ± 7.1^∆∆	6.9 ± 3.7^∆∆	6.9 ± 3.7^∆∆	—	—	—
	H9N2ⁱ	0	109.8 ± 5.9	103.6 ± 5.8	87.3 ± 4.0^∆	55.4 ± 4.1^∆∆	54.4 ± 5.3^∆∆	138.4 ± 7.4	136.5 ± 4.8	124.1 ± 8.6
Low therapeutic dose	ATRA1 + H9N2^j	1	87.5 ± 12.4^#	63.9 ± 7.7^##**	44.5 ± 11.8^##**	79.8 ± 14.2	86.7 ± 14.8*	104.2 ± 14.9*	127.0 ± 12.4	133.7 ± 7.2
Medium therapeutic dose	ATRA2 + H9N2^k	5	32.0 ± 5.3^##**	36.8 ± 7.2^##**	52.2 ± 7.2^##**	78.6 ± 10.6*	86.8 ± 8.5**	109.5 ± 5.8**	136.1 ± 10.2	161.1 ± 11.1
	ATRA3 + H9N2^l	10	32.4 ± 5.2^##**	56.6 ± 7.4^##**	67.9 ± 9.5^##	79.1 ± 10.2*	100.5 ± 7.8**	117.7 ± 3.8*	118.6 ± 2.6*	134.0 ± 5.0^#
High therapeutic dose	ATRA4 + H9N2^m	20	46.4 ± 6.7^##**	43.4 ± 11.2^##**	36.6 ± 8.4^##**	43.6 ± 8.3	59.6 ± 9.2	74.5 ± 9.8**	96.8 ± 6.1**	97.7 ± 6.4*
Toxic dose	ATRA5 + H9N2ⁿ	40	34.9 ± 7.6^##**	39.0 ± 8.3**	54.6 ± 6.2**	41.8 ± 8.0^#	43.4 ± 7.8^##	44.4 ± 7.6^##**	46.1 ± 7.4^#**	—
	ATRA6 + H9N2^o	60	24.5 ± 7.5^##**	17.9 ± 6.5**	22.6 ± 7.4**	15.7 ± 5.8**	22.6 ± 6.6**	18.2 ± 5.9**	—	—
	ATRA7 + H9N2^p	80	21.2 ± 5.7^#**	9.1 ± 3.9**	6.6 ± 2.9**	4.8 ± 2.5**	3.0 ± 1.9**	—	—	—

Data are presented as mean of the change rate of food intake (%) ± SD. Change rate of food intake (%) = food intake per day/initial food intake × 100%. n = 10–11. Statistical analyses were performed with one-way ANOVA and Bonferroni correction. ATRA group or H9N2 group compared with blank group: ∆, P < 0.05; ∆∆, P < 0.01; ATRA + H9N2 group compared with ATRA group: ^#P < 0.05; ^##P < 0.01; ATRA + H9N2 group compared with H9N2 group: *P < 0.05; **P < 0.01. a: Blank, mice administered sterile PBS inoculation and cottonseed oil injection; b-h: ATRA1-ATRA7, mice administered sterile PBS inoculation and ATRA injection (1, 5, 10, 20, 40, 60, and 80 mg/kg, respectively); i: H9N2, mice administered H9N2 virus (10⁵ TCID₅₀) inoculation and cottonseed oil injection; j-p: ATRA1 + H9N2-ATRA7 + H9N2, mice administered H9N2 virus (10⁵ TCID₅₀) inoculation and ATRA injection (1, 5, 10, 20, 40, 60, and 80 mg/kg, respectively). ATRA, all-trans retinoic acid; TCID₅₀, median tissue culture infective dose

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