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 1 Effects of different doses of ATRA and H9N2 virus on the body weight of 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	104.0 ± 2.9	104.6 ± 3.3	104.0 ± 2.9	104.4 ± 3.1	104.6 ± 3.1	105.2 ± 3.9	106.7 ± 3.3	112.7 ± 3.1
Low therapeutic dose	ATRA1^b	1	103.9 ± 1.1	104.9 ± 1.1	105.4 ± 1.3	104.6 ± 1.4	104.7 ± 1.8	105.7 ± 1.9	107.6 ± 2.5	112.7 ± 2.3
Medium therapeutic dose	ATRA2^c	5	104.7 ± 1.9	105.2 ± 1.9	105.7 ± 2.1	104.6 ± 2.2	104.9 ± 1.8	106.0 ± 1.9	108.2 ± 2.4	111.1 ± 2.8
	ATRA3^d	10	104.4 ± 1.7	104.7 ± 2.0	104.6 ± 2.1	104.3 ± 2.6	104.7 ± 1.8	105.5 ± 2.0	105.8 ± 2.1	108.9 ± 2.6
High therapeutic dose	ATRA4^e	20	100.8 ± 3.2	100.3 ± 2.8^∆	100.2 ± 2.7^∆	98.8 ± 2.6^∆∆	99.0 ± 3.1^∆∆	99.3 ± 3.8^∆∆	101.3 ± 3.1^∆∆	105.4 ± 2.2^∆
Toxic dose	ATRA5^f	40	97.6 ± 2.7^∆∆	93.9 ± 3.2^∆∆	90.0 ± 3.6^∆∆	85.1 ± 4.3^∆∆	81.6 ± 4.0^∆∆	76.5 ± 4.9^∆∆	76.3 ± 4.8^∆∆	—
	ATRA6^g	60	96.1 ± 1.5^∆∆	90.6 ± 2.1^∆∆	87.5 ± 3.0^∆∆	83.2 ± 2.9^∆∆	79.5 ± 2.7^∆∆	74.7 ± 2.6^∆∆	73.9 ± 3.3^∆∆	—
	ATRA7^h	80	92.5 ± 2.5^∆∆	87.1 ± 2.3^∆∆	82.1 ± 2.5^∆∆	76.5 ± 3.0^∆∆	73.4 ± 2.8^∆∆	—	—	—
	H9N2ⁱ	0	100.2 ± 1.2^∆	99.6 ± 1.3^∆∆	97.5 ± 1.2^∆∆	93.2 ± 2.5^∆∆	90.9 ± 2.8^∆∆	103.5 ± 3.7	105.4 ± 3.1	110.8 ± 4.5
Low therapeutic dose	ATRA1 + H9N2^j	1	98.8 ± 5.7	95.6 ± 7.7^#	93.2 ± 7.6^##	91.0 ± 9.5^##	95.9 ± 12.3	100.2 ± 13.7	102.6 ± 10.9	109.9 ± 5.1
Medium therapeutic dose	ATRA2 + H9N2^k	5	94.7 ± 2.9^##**	91.5 ± 3.1^##**	90.6 ± 5.6^##*	93.0 ± 8.8^#	94.3 ± 11.0	97.3 ± 12.4	101.6 ± 12.0	113.9 ± 5.4
	ATRA3 + H9N2^l	10	93.5 ± 2.3^##**	91.8 ± 3.1^##**	92.2 ± 4.1^##*	92.6 ± 6.2^##	95.0 ± 7.0^#	97.5 ± 7.4^#	100.3 ± 7.6	109.5 ± 5.3
High therapeutic dose	ATRA4 + H9N2^m	20	91.9 ± 4.1^##**	90.4 ± 4.1^##**	89.5 ± 3.8^##**	90.2 ± 4.3^##	92.3 ± 4.2^##	92.9 ± 4.1^##**	95.3 ± 4.2^##**	103.3 ± 3.4**
Toxic dose	ATRA5 + H9N2ⁿ	40	89.2 ± 6.0^##**	88.8 ± 7.1**	88.4 ± 7.3*	85.1 ± 6.6**	85.2 ± 4.0**	82.0 ± 4.6**	79.0 ± 3.6**	—
	ATRA6 + H9N2^o	60	94.1 ± 2.3**	90.1 ± 3.4**	86.9 ± 3.5**	81.6 ± 2.9**	77.5 ± 4.3**	73.3 ± 2.9**	—	—
	ATRA7 + H9N2^p	80	90.5 ± 3.3**	86.1 ± 2.8**	81.2 ± 3.0**	75.6 ± 3.2**	70.7 ± 0.8**	—	—	—

Data are presented as mean of the rate of weight change (%) ± SD. Rate of weight change (%) = daily weight/initial weight × 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 receiving sterile PBS inoculation and cottonseed oil injection; b–h: ATRA1-ATRA7, mice receiving sterile PBS inoculation and ATRA injection (1, 5, 10, 20, 40, 60, and 80 mg/kg, respectively); i: H9N2, mice receiving H9N2 virus (10⁵ TCID₅₀) inoculation and cottonseed oil injection; j–p: ATRA1 + H9N2-ATRA7 + H9N2, mice receiving 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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