Host genomic HIV restriction factors modulate the response to dendritic cell-based treatment against HIV-1

Figures & data

Table 1. Results of polymorphisms association analysis in 18 HIV+ patients underwent DC-based immune treatment against HIV-1 classified in good responder (GR) and weak or transient responder (WTR) according to Lu et al.³

Gene	Polymorphism	GR (n = 8)	WTR (n = 10)	P value	OR (CI 95%)
APOBEC3G	rs3736685
	C	2	1	0.574	2.64 (0.13–168.21)
	T	14	11
	C/C	0	0	0.396
	C/T	2	1
	T/T	6	9
	rs2294367
	G	7	9	1.0	0.95 (0.21–4.32)
	C	9	11
	C/C	3	2	0.375
	C/G	3	7
	G/G	2	1
CCL4	rs1719153
	T	6	8	1.0	0.90 (0.19–4.21)
	A	10	12
	T/T	0	0	0.800
	A/T	6	8
	A/A	2	2
	rs1719134
	G	4	4	1.0	1.32 (0.20–8.72)
	A	12	16
	A/A	5	6	0.789
	A/G	2	4
	G/G	1	0
CCL5	rs2280789
	G	0	4	0.113	0 (0–1.79)
	A	16	16
	G/G	0	0	0.092
	A/G	0	4
	A/A	8	6
	rs2107538
	T	2	6	0.257	0.34 (0.03–2.37)
	C	14	14
	T/T	0	0	0.132
	C/T	2	6
	C/C	6	4
CCR5	∆32
	wt	16	15	1	0 (0–48.71)
	∆32	0	1
	wt/wt	8	9	1
	wt/∆32	0	1
	∆32/∆32	0	0
CUL5	rs7117111
	A	6	9	0.741	0,74 (0.15–3.38)
	G	10	11
	A/A	0	3	0.142
	A/G	6	3
	G/G	2	4
	rs11212495
	G	1	5	0.196	0.21 (0.00–2.19)
	A	15	15
	G/G	0	1	0.588
	A/G	1	3
	A/A	7	6
	rs7103534
	C	0	2	0.492	0 (0–6.64)
	T	16	18
	C/C	0	0	0.477
	C/T	0	2
	T/T	8	8
SDF1	rs2234358
	T	6	7	1	1.11 (0.23–5.35)
	G	10	13
	T/T	0	2	0.214
	G/T	6	3
	G/G	2	5
HLA-C	rs10484554
	T	4	2	0.374	2.91 (0.35–36.98)
	C	12	18
	T/T	2	0	0.2288
	C/T	0	2
	C/C	6	8
	rs9264942
	C	6	6	0.730	1.39 (0.28–7.0)
	T	10	14
	C/C	1	1	0.868
	C/T	4	4
	T/T	3	5
IFNG	rs2069709
	A	0	2	0.492	0 (0–6.64)
	C	16	18
	A/A	0	1	1
	A/C	0	0
	C/C	8	9
PARD3B	rs11884476
	G	5	2	0.204	3.93 (0.53–48.04)
	C	11	18
	G/G	0	1	6.5 exp-3*	* co-dominant and over-dominant
	C/G	5	0
	C/C	3	9
Prox1	rs17762192
	C	7	10	0.749	0.78 (0.17–3.51)
	G	9	10
	C/C	2	2	0.607
	C/G	3	6
	G/G	3	2
CXCL12	rs1801157
	T	4	3	0.675	1.86 (0.26–15.08)
	C	12	17
	T/T	1	1	0.665
	C/T	2	1
	C/C	5	8
TRIM5	rs16934386
	G	1	0	0.444	inf (0.03–inf)
	A	15	20
	G/G	0	0	0.444
	A/G	1	0
	A/A	7	10
	rs10838525
	C	0	0	monomorphic	monomorphic
	T	16	20
	C/C	0	0	monomorphic	monomorphic
	C/T	0	0
	T/T	8	10
	rs3740996				1.79 (0.31–11.26)
	G	5	4	0.470
	A	11	16
	GG	0	1	0.145
	AG	5	2
	AA	3	7
ZNRD1	rs3869068
	T	5	3	0.422	2.51 (0.39–19.52)
	C	11	17
	TT	1	0	0.472
	CT	3	3
	CC	4	7
	rs8321
	C	0	0	monomorphic	monomorphic
	A	16	20
	CC	0	0	monomorphic	monomorphic
	AC	0	0
	AA	8	10

Figure 1. Plasma viral load (PVL) reduction and cellular response in 18 HIV+ patients who’s underwent DC-based immune treatment against HIV-1 according to PARD3B rs11884476 genotypes. Change in PVL expressed as log change (∆log), change in CD4+ and CD8+ cells counts (∆cells/µl) and change in percentage of CD4+ and CD8+ cells producing IFN-ϒ (∆%) are reported for the 18 HIV+ patients included in the phase I clinical trial of DC-based immune-therapy³ classified according to PARD3B rs11884476 genotypes. The data, obtained from Lu et al.,³ represent difference (∆) between values presented 1 y after immunization and before the starting of the trial. Individual data and media were reported. (A) Plasma viral load (PVL). Individual blood CD4+ (B) and CD8+ (C) cell counts. (D and E) Intracellular IFN-γ detection of T cells following stimulation with HIV-1-pulsed DC. Percentage of total CD4+ (D) or CD8+ (E) cell secreting IFN-γ is reported. T test analysis was performed between C/C and C/G groups and between C/C+G/G and C/G groups according to an over-dominant model. Being unique value the G/G has been excluded from the analysis. *P < 0.05; **P < 0.01.

Figure 2. Possible interactions between PARD3B and SMAD proteins influencing TGFß signaling. The two hypotheses concerning the dual role of PARD3 in terms of viral replication control or DC-mediated lymphocytes activation are reported according to rs11884476 genotypes (2A: wild type C/C genotype; 2B: G/G genotype). The up or downregulation of TGFß signaling and the consequences in terms of AIDS progression or DC immune-regulation are evidenced in red rectangles.

Lu W, Arraes LC, Ferreira WT, Andrieu JM. Therapeutic dendritic-cell vaccine for chronic HIV-1 infection. Nat Med 2004; 10:1359 - 65; http://dx.doi.org/10.1038/nm1147; PMID: 15568033

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