Ability of HIV-1 Nef to downregulate CD4 and HLA class I differs among viral subtypes

Retrovirology

Table 3 Amino acids associated with intra-subtype Nef HLA-I downregulation function

Subtype	Codon^a	AA^b	Cons.^c	Function^d		No. of samples^e		p-value	q-value
Subtype	Codon^a	AA^b	Cons.^c	+ AA	- AA	+ AA	-AA	p-value	q-value
A	3	G	G	82.3	87.1	71	23	0.007	0.4
	9	R	S	94.5	83.1	5	84	0.02	0.4
	11	V	V	81.5	87.9	74	16	0.007	0.4
	83	G	G	80.6	87.0	63	31	0.01	0.4
	89	F	H	90.8	82.4	15	79	0.01	0.4
	105	R	K	78.4	85.0	22	72	0.02	0.4
	120	Y	Y	82.4	86.7	56	38	0.02	0.4
	168	M	I	87.1	81.9	23	71	0.02	0.4
	191	L	L	81.0	87.1	57	37	0.005	0.4
	196	Q	R	80.2	86.2	34	60	0.008	0.4
B	8	R	S	98.2	94.6	28	56	0.006	0.2
	8	S	S	94.3	98.0	38	46	0.0009	0.2
	14	P	P	94.4	97.7	58	34	0.01	0.2
	28	A	D	101.5	95.0	7	85	0.004	0.2
	65	D	E	89.7	96.4	8	84	0.02	0.3
	65	E	E	96.4	87.3	83	9	0.009	0.2
	89	F	H	63.7	95.6	5	87	0.03	0.4
	89	H	H	95.7	60.8	86	6	0.007	0.2
	98	D	E	99.7	95.1	6	86	0.02	0.3
	98	E	E	95.0	100.6	85	7	0.007	0.2
	105	Q	K	91.0	96.5	18	74	0.03	0.4
	153	I	V	90.5	96.7	16	75	0.007	0.2
	153	V	V	96.7	90.0	74	17	0.003	0.2
	198	K	L	98.8	94.7	19	73	0.01	0.2
	202	F	Y	99.4	95.0	9	83	0.01	0.2
	202	Y	Y	95.0	99.4	83	9	0.01	0.2
C	9	S	S	78.1	96.6	66	5	0.01	0.3
	40	H	H	84.0	72.3	38	36	0.005	0.3
	40	Y	H	72.3	84.0	34	40	0.003	0.3
	102	H	Y	56.2	81.8	12	62	0.02	0.4
	105	K	K	83.5	71.1	53	21	0.005	0.3
	105	R	K	57.8	82.5	15	59	0.01	0.3
	108	D	E	71.1	83.7	37	37	0.01	0.3
	108	E	E	83.7	71.1	37	37	0.01	0.3
	182	Q	K	49.6	80.7	8	66	0.01	0.3

^aNumbered according to HXB2.
^b Amino acid variants associated with differences in HLA-I downregulation function. Only common amino acid variants (present at n ≥ 5 in each subtype) were investigated.
^cConsensus amino acid for the codon and subtype indicated.
^dMedian HLA-I downregulation function (expressed as a percentage relative to SF2) of Nef sequences with (+AA) and without (-AA) the amino acid variant.
^eNumber of sequences with (+AA) and without (-AA) the amino acid variant. Amino acid totals vary, as gaps in the alignment are considered missing data.
A similar intra-subtype analysis was performed to identify Nef amino acids associated with CD4 downregulation function; no associations q < 0.4 were identified using this approach.

ISSN: 1742-4690