Possible influence of the mutant CCR5 allele on vertical transmission of HIV-1

A possible correlation between the rate of vertical transmission of HIV-1 and the presence of the defective HIV co-receptor gene Δ32ccr5 in the chromosomes of infants born to HIV-positive mothers was assessed. The prevalence and genotypic distribution of the Δ32ccr5 gene were studied in 451 uninfected and 225 HIV-1-infected adults and 79 children born to HIV-1-positive mothers in Austria (45 uninfected and 34 infected by vertical transmission). As expected in a Caucasian population, the Δ32ccr5 allele was found in uninfected Austrians at a frequency of 10% (17.3% heterozygotes and 1.3% Δ32ccr5/Δ32ccr5 homozygotes, consistent with the expected Hardy-Weinberg distribution). The mutant allele frequency was 11.1% in uninfected children (17.8% heterozygotes, 2.2% homozygotes) and 9.6% in HIV-positive adults (19.1% heterozygotes but no Δ32ccr5/Δ32ccr5 homozygotes). Among the group of 34 vertically infected children, however, there were only two heterozygotes and no Δ32ccr5/Δ32ccr5 homozygotes, corresponding to a significantly reduced mutant allele frequency of 2.9% (P = 0.05 compared to HIV-negative children). These results suggest that CCR5/Δ32ccr5 heterozygous children are less susceptible to vertical transmission of HIV-1. The data also support the hypothesis that Δ32ccr5 homozygous individuals are resistant to HIV-1 infection. J. Med. Virol. 55:51–55, 1998. © 1998 Wiley-Liss, Inc.     

Dominant effects of CCR2-CCR5 haplotypes in HIV-1 disease progression

Three haplotypes for the CCR2-CCR5 region previously have been shown to affect AIDS progression; however, it is not known if the protective and accelerating effects of the haplotypes are relatively constant throughout infection or exert their effects early or late in HIV type 1 infection. The authors report the relative contributions to AIDS progression of CCR2 64I, CCR5 Delta32, and the CCR5 promoter haplotype +.P1.+ in the GRIV cohort, which included patients representing the extremes of the distribution for AIDS progression: rapid progressors (RP) who developed CD4 T-cell counts of <300/ mm within 3 years after the last HIV-1-seronegative test and slow progressors (SP) who were HIV-1 infected for > or =8 years with CD4 T-cell counts of >500/mm. Comparing the RP with a seroconverter control group including intermediate progressors to AIDS, we observed the early protective effect of CCR5 Delta32 (odds ratio = 0.25; P = 0.007) was similar in strength to the early susceptible effect of CCR5 +.P1.+ (odds ratio = 2.1, P = 0.01). Comparison of the intermediate control group to the SP showed weaker and less significant odd ratios, suggesting that the effect of these factors tended to be stronger on early progression; the tendency towards a disproportionately early effect was significant for CCR5 Delta32 (P = 0.04) but not for CCR5 +.P1.+ (P = 0.12). Follow-up of SP demonstrated that these polymorphisms have little effect after 8 years, because the subset of SP who had progression after study entry had the same genotype distribution as the global population of SP, suggesting that factors other than CCR5 or CCR2 genetic variants must be responsible for the long-term maintenance of nonprogression.     

Genetic variation at the chemokine receptors CCR5/CCR2 in myocardial infarction

Our objective was to examine the association between myocardial infarction (MI) and two DNA-polymorphisms at the proinflammatory chemokine receptors CCR2 (I64V) and CCR5 (32 bp deletion, (Delta)ccr5), defining if these polymorphisms influence the age for the onset of MI. A total of 214 patients with an age at the first MI episode <55 years, 96 patients that suffered the first MI episode when older than 60 years, and 360 population controls were polymerase chain reaction genotyped for the CCR2-V64I and CCR5-Delta32/wt polymorphisms. Patients and controls were male from the same Caucasian population (Asturias, northern Spain). The frequency of the Deltaccr5 allele was significantly higher in controls compared to patients <55 years (P = 0.004), or in patients >60 years compared to patients <55 years (P = 0.002). Taking the patients >60 years as the reference group, non-carriers of the (Delta)ccr5-allele would have a three-fold higher risk of suffering an episode of MI at <55 years of age (OR = 3.06; 95% CI = 1.46-6.42). Gene and genotype frequencies for the CCR2 polymorphism did not differ between patients <55 years and controls or patients >60 years. Our data suggest that the variation at the CCR5 gene could modulate the age at the onset of MI. Patients carrying the (Delta)ccr5-allele would be protected against an early episode of MI. CCR5 and the CCR5-ligands are expressed by cells in the arteriosclerotic plaque. Thus, the protective role of (Delta)ccr5 could be a consequence of an attenuated inflammatory response, that would determine a slower progression of the arteriosclerotic lesion among (Delta)ccr5-carriers. Our work suggests that the pharmacological blockade of CCR5 could be a valuable therapy in the treatment of MI.     

CCR5 genetic variants and epidemiological determinants for HPV infection and cervical premalignant lesions

Human papillomavirus (HPV) infection can lead to the development of productive epithelial lesions and cervical cancer. Most cervical HPV infections are solved by cell‐mediated immunity within 1–2 years, and it is known that chronic inflammation predisposes to lesions progression and tumour development. In this context, we highlight the CC chemokine receptor 5 (CCR5) which is involved in leucocytes chemotaxis to sites of inflammation, controlling the immune response. The CCR5 rs333 genotyping of 164 HPV infected women and 185 non‐infected women was performed using polymerase chain reaction (PCR). HPV infection was more frequent among women under 34 years old (p < 0.001), single (p = 0.001), that received 1 minimum wage or less (p = 0.002), tobacco smokers (p = 0.007), who had the first sexual intercourse before 17 years old (p = 0.038) and that had 4 or more sexual partners during lifetime (p = 0.001). No significant difference regarding genotypes and alleles distribution according to HPV infection was observed. CCR5/CCR5 genotype was observed in 94.1% of HPV non‐infected women and in 89% of infected ones, CCR5/Δ32 in 5.9% of HPV infected and in 10.4% of non‐infected women, and Δ32/Δ32 was observed in only one (0.6%) infected patient. CCR5 genotypes were also not associated with cervical lesions development among HPV infected women (p = 0.167). Since CCR5 may control the antitumour immune response and cervical lesions and the studied rs333 polymorphism is not very frequent, other studies are necessary, in order to establish CCR5 role on HPV infection and squamous intraepithelial lesions development.     

Effects of the CCR5-Δ32 Mutation on Hepatitis C Virus-Specific Immune Responses in Patients with Haemophilia

In hepatitis C virus (HCV) infection antiviral T cells express the CC chemokine receptor 5 (CCR5). Their recruitment to the liver is an important step in the immune response. A 32 base pair deletion in the CCR5 gene leads to reduced expression and total loss of CCR5 in CCR5-Δ32 heterozygous and homozygous subjects, respectively. However, the role of this mutation for antiviral immunity remains unclear. Here, we analysed proliferation, IFN-γ and IL-4 secretion (ELISpot) induced by the HCV antigens core, NS3, NS4, and NS5a in 21 anti-HCV-positive haemophiliac patients in relationship to their CCR5 genotypes (CCR5 wildtype n = 10, CCR5-Δ32 heterozygous n = 5 and CCR5-Δ32 homozygous n = 6). Furthermore, T cell migration in response to the CCR5 ligands CCL3, –4 and –5 was studied. Overall IFN-γ responses to HCV proteins were only slightly greater in CCR5 wild-type patients than in CCR5-Δ32 carriers (0.6 versus 0.24 SFC/10⁴ PBMC; p = 0.043). This difference was consistently seen with all tested HCV antigens. In contrast, neither T cell migration, nor PBMC proliferation, nor IL-4 production differed between CCR5 genotypes. Interruption of the CCR5 signalling pathway due to CCR5-Δ32 may potentially result in subtle reduction of HCV specific IFN-γ responses in anti-HCV-positive haemophiliac patients.     

Human Immunodeficiency Virus Type 1 Disease Progression, CCR5 Genotype, and Specific Immune Responses

The correlation among the presence of a 32-bp deletion in the CC-chemokine receptor 5 (CCR5) gene, disease progression, and human immunodeficiency virus type 1 (HIV-1)-specific immune responses was analyzed for a cohort of 79 Caucasian HIV-1-infected patients. The CCR5 genotype (CCR5/CCR5 = wild type/wild type or Δ32CCR5/CCR5 = 32-bp deletion/wild type) in peripheral blood mononuclear cells was determined by PCR, followed by sequencing of both wild-type and Δ32CCR5 gene fragments. HIV-1-specific humoral responses to gp41 and V3_MN peptides were determined by enzyme immunoassays. The prevalence of the Δ32CCR5 allele was lower among 37 patients with rapid progression (progression to AIDS or to a CD4 cell count of <200 × 10⁶/liter in less than 9 years; P < 0.01) compared to that for 42 patients with slow progression (no AIDS and CD4 cell count of >200 × 10⁶/liter after at least 9 years from infection) or to that for 25 non-HIV-1-infected Swedish blood donors (P < 0.05). No differences were observed in the wild-type CCR5 sequences between the different groups of patients. For three analyzed patients, the 32-bp Δ32CCR5 gene deletions were identical. The antibody titers against gp41 and a V3_MN peptide in patients with the Δ32CCR5/CCR5 genotype were not significantly different from those in pair-matched CCR5/CCR5 controls. However, in 13 analyzed patients, a stronger serum neutralizing activity was associated with the Δ32CCR5/CCR5 genotype. Thus, a CCR5/CCR5 genotype correlates with a shortened AIDS-free HIV-1 infection period and possibly with a worse neutralizing activity, without an evident influence on the antibody response to two major antigenic regions of HIV-1 envelope.     

IL6 and FAS/FASL gene polymorphisms may be associated with disease progression in HIV-1-positive ethnically mixed patients

The progression of AIDS depends on the complex host and virus interactions. The most important disease progression hallmarks are immune activation and apoptosis. In this study, we address the prevalence of polymorphisms related to proinflammatory and apoptotic genes, such as IFNG (+874T/A), TNF (308G/A), IL6 (−174G/C), IL8 (−251A/T), FAS (−670A/G), and FASL (−124A/G) in 160 ethnically mixed HIV-1-infected patients from multicentre cohorts with different clinical outcomes (13 elite controllers [EC], 66 slow long-term non-progressors [LTNPs], and 81 progressors [P]). The genotyping was accomplished by TaqMan-qPCR. Among all the polymorphisms analyzed in the cytokines, the IL6 −174G/C polymorphism showed a higher frequency of GG genotype in the LTNP and LTNP+EC groups as compared to the P group. Moreover, there was a significantly higher frequency of the G allele in the LTNP and LTNP+EC groups as compared to the P group. On the other hand, the levels of CD4⁺ T lymphocytes were higher among individuals showing the AA and AG genotypes for the FASL −124A/G polymorphism as compared to the GG genotype. Furthermore, the AG and AA genotypes were more frequent, as compared to the GG genotype, in individuals showing a lower viral load. In contrast, for the FAS −670A/G polymorphism, a significantly higher viral load was observed in individuals with the AG genotype as compared to the GG genotype. In conclusion, we found three genetic allelic variants of the IL6 −174G/C, FASL −124A/G, and FAS −670A/G polymorphisms that were related to disease progression and immunological and virological markers in cohorts of HIV-1-positive ethnically mixed patients.     

The CCR5Δ32 allele is associated with reduced liver inflammation in hepatitis C virus infection

CCR5Δ32 is a deletion mutation in the chemokine receptor CCR5. Liver inflammatory activity was found to be significantly reduced (P = 0.005) in Jewish Israeli patients infected with the hepatitis C virus (HCV) carrying the CCR5Δ32 allele. The CCR5Δ32 allele does not alter susceptibility to HCV infection; however, it may play a role in the progression and outcome of the disease.     

中国HIV-1感染疾病长期不进展者CCR2-64I、SDF1-3’A和CCR5Δ32的基因变异研究

目的 探讨CCR2-641、SDF1-3’A、CCR5Δ32基因变异对中国HIV—1感染疾病长期不进展者（long-term nonprogressors，LTNPs）疾病进程的影响。方法 收集17例中国HIV-1感染LTNPs和39例中国HIV-1感染疾病典型进展者（typical progressors，TPs）的抗凝全血标本，用全自动核酸提取仪提取基因组DNA，采用PCR／RFLP技术对CCR2、SDF1、CCR5基因进行检测分析。结果 LTNP组的CCR2-64I、SDF1-3’A基因突变率分别为50％和62．5％，TP组的CCR2-64I和SDF1-3’A基因突变率分别为23．08％、33．33％，LTNP组CCR2—64I、SDF1-3’A基因突变率明显高于TP组（P〈0．05）；LTNP组有1例CCR5Δ32杂合突变，未发现纯合变异，而TP组未发现CCR5Δ32突变。结论 CCR2-64I、SDF1-3’A和CCR5Δ32基因突变可能是中国HIV-1感染者疾病长期不进展的保护性因素之一。     

CCR5基因启动子59029位点单核苷酸多态性与HIV-1疾病进展关系的Meta分析

目的探讨CCR5基因启动子59029位点单核苷酸多态性（SNPs）与HIV-1感染者疾病进展的关系。方法按照制定的检索策略,在PubMed、CBM、VIP等数据库检索有关CCR5基因启动子59029位点SNPs与HIV-1感染者疾病进展关系的研究,按照纳入和排除标准选取文献,评价文献质量,提取相关数据。用Stata 10.0统计软件对数据进行Meta分析。结果按照纳入和排除标准,共纳入4个病例对照研究,其中长期不进展者（LTNP）总例数375人,快速进展者（RP）总例数282人。Meta分析结果显示,在排除了CCR5Δ32和CCR2-64I突变后,RP组的59029A/A纯合子基因型频率是0.235,高于LTNP组的0.144,两者差异具有统计学意义（Z=2.37,P=0.018）,OR及95%CI是3.441（1.236,9.582）。RP组的59029A等位频率是0.513,也高于LTNP组的0.370（Z=3.13,P=0.002）。结论 CCR5基因启动子59029A等位与HIV-1疾病的快速进展相关。     

Differential prevalence of the HLA-C -- 35 CC genotype among viremic long term non-progressor and elite controller HIV+ individuals

Susceptibility to HIV infection and disease progression are complex traits modulated by environmental and genetic factors, affecting innate and adaptive immune responses, among other cellular processes. A single nucleotide polymorphism (SNP) 35 kb upstream of the HLA-C gene locus (-35C/T) was previously shown to correlate with increased HLA-C expression and improved control of HIV-1. Here, we genotyped the -35C/T SNP in 639 subjects (180 uninfected patients, 304 HIV progressors and 155 LTNP) and confirmed the association of the -35C/T variant with the LTNP phenotype. The genotype frequencies in the general population subjects did not differ significantly from those seen in HIV progressors (p-value=0.472). However, a significant higher frequency of the protective CC genotype was identified when LTNP were compared either with HIV progressors alone (p-value<0.0001) or progressors and uninfected subjects together (p-value<0.0001). When considering aviremic LTNP alone (elite controllers; viral load below 50 copies/ml), the -35 CC genotype was not overrepresented compared to HIV progressors. Conversely, a significant association was found with the viremic LTNP groups (viral loads below 10,000 copies/ml). These results suggest that other factors alone or in combination with the -35 CC genotype may play an important role in differentiating the elite controller status from LTNP. Combination of different genetic variants may have additive or epistatic effects determining the HIV course of infection.     

Adverse effect of the CCR5 promoter -2459A allele on HIV-1 disease progression

HIV positive individuals heterozygous for a 32 basepair deletion in the CCR5 encoding gene (CCR5 Delta32) have a reduced number of CCR5 receptors on the cell surface and a slower progression towards AIDS and death. Other human polymorphisms, such as the CCR2 64I and the CCR5 promoter -2459 A/G transition that has been discovered recently, have also been shown to influence HIV progression. Since genetic linkages make these polymorphisms interdependent variables, the aim of the present study was to isolate and evaluate the effect on HIV disease progression for each of these mutations independently. Genotypes were determined in 119 individuals enrolled in the Copenhagen AIDS Cohort. When including the concurrent effects of the CCR5 Delta32 and CCR2 64I mutations, homozygous carriers of the CCR5 promoter -2459A allele had a significantly faster progression towards death than heterozygous A/G individuals (P = 0.03), whereas this adverse effect was not significant when comparing A/A and G/G individuals. However, independent analysis revealed a significant adverse effect of the CCR5 promoter -2459A allele. Homozygous carriers of the -2459A allele that lack the protective effects of the CCR5 Delta32 and CCR2 64I mutations were found to have a median survival of 6.0 years, whereas carriers of the -2459G allele had a median survival of 9.4 years (P < 0.01).     

Hepatitis C virus (HCV) coinfection in a cohort of HIV positive long-term non-progressors: possible protective effect of infecting HCV genotype on HIV disease progression.

BACKGROUND AND OBJECTIVE: Hepatitis C virus (HCV) infection is frequent in HIV-positive subjects. We evaluated the potential impact of HCV coinfection and other determinants on HIV disease progression in a cohort of long-term non-progressors (LTNPs). STUDY DESIGN: We studied immunological and virological factors in a cohort of 49 LTNPs, 23 of whom progressed during the follow-up (late progressors; LPs). RESULTS: HCV coinfection was detected in 19/26 LTNPs and 15/23 LPs. Univariate analysis showed that HIV viral load was associated with disease progression (P=0.04), and time-to-event analysis indicated that HCV genotype 1 significantly correlated with LTNP status (P=0.031). At multivariate analysis, HIV viremia at study entry remained independently associated with LTNP status (P=0.049). When the most represented genotypes (1 and 3a) were considered in the model, genotype 3a infection (P=0.034) and gender (P=0.035) emerged as independent variables related to HIV disease progression, whereas HIV viral load disappeared. CONCLUSIONS: In addition to HIV viremia, coinfection with different HCV genotypes and gender may affect LTNP status.     

Marked differences in CCR5 expression and activation levels in two South African populations

The chemokine receptor CCR5 is pivotal in determining an individual's susceptibility to HIV-1 infection and rate of disease progression. To establish whether population-based differences exist in cell surface expression of CCR5 we evaluated the extent of CCR5 expression across all peripheral blood cell types in individuals from two populations, South African Africans (SAA) and South African Caucasians (SAC). Significant differences in CCR5 expression, both in number of CCR5 molecules per cell (density) and the percentage of CCR5-expressing cells, were observed between the two study groups, within all cell subsets. Most notably, the percentage of all CCR5(+) cell subsets was significantly lower in SAC compared with SAA individuals (P < 0·01) among natural killer (NK) -cell subsets (CD56(+) , CD16(+) CD56(+) and CD56(dim) ) whereas CCR5 density was significantly higher in SAC compared with SAA individuals in CCR5(+) CD8(+) T-cell subsets and CCR5(+) NK-cell subsets (CD56(+) , CD16(+) CD56(+) and CD56(dim) ) (all P < 0·05). These relationships were maintained after exclusion of CCR5Δ32 heterozygous individuals (n = 7) from the SAC dataset. The SAA individuals exhibited significantly higher cell activation levels, as measured by HLA-DR expression, than SAC individuals in CD4(+) T-cell subsets (P = 0·002) and CD56(+) NK-cell subsets (P < 0·001). This study serves to demonstrate that ethnically divergent populations show marked differences in both cell activation and CCR5 expression, which are likely to impact on both susceptibility to HIV-1 infection and the rate of HIV-1 disease progression.     

CCR2 and CCR5 genes polymorphisms in benign prostatic hyperplasia and prostate cancer

Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are two chronic conditions, very common in aged men, that have been associated to inflammatory process. Chemokines and their receptors are recognized as critical mediators of inflammatory responses, they regulate immune cell migration and are implicated in tumor pathogenesis. The impact of two chemokine receptor gene polymorphisms, CCR2-64I (rs1799864) and CCR5-Δ32 (rs333), was evaluated in BPH and PCa. 385 DNA samples (130 BPH, 136 PCa, 119 healthy control) were genotyped. The allele frequencies were similar among control, BPH and PCa groups. Median of serum PSA levels was different between groups: 0.79, 1.45 and 6.91 ng/mL in control, BPH and PCa groups, respectively (all p < 0.001). The prostate volume median was 20.00 cm³ in the control group, thus, lower than BPH (35.35 cm³) and PCa (35.80 cm³) (both p < 0.001), nevertheless no statistical significant difference was observed between BPH and PCa patients (p = 0.172). Remarkably, CCR2-64I was a protective factor to PCa when compared with BPH (OR = 0.550; 95%CI = 0.311–0.975), although the statistically significant difference was lost after correction for multiple comparisons. No significant associations of CCR5-Δ32 variant were observed with BPH, PCa or PCa clinicopathologic status. Our data suggest the influence of CCR2-64I variant in the development of prostate cancer.     

Chemokine receptor CCR5 polymorphisms and Chagas' disease cardiomyopathy

In this study we investigated the possible role of two CCR5 gene polymorphisms, CCR5Delta32 deletion and CCR5 59029 A-->G promoter point mutation, in determining the susceptibility to Trypanosoma cruzi infection as well as in the development of chagasic heart disease. These CCR5 polymorphisms were assessed in 85 seropositive (asymptomatic, n=53; cardiomyopathic, n=32) and 87 seronegative individuals. The extremely low frequency (0.009) of the CCR5Delta32 allele in our population did not allow us to analyse its possible influence on T. cruzi infection. We found no differences in the distribution of CCR5 59029 promoter genotype or phenotype frequencies between total chagasic patients and controls. However, we observed that the CCR5 59029-A/G genotype was significantly increased in asymptomatic with respect to cardiomyopathic patients (P=0.02; OR=0.33, 95% CI 0.10-0.94). In addition, the presence of the CCR5 59029-G allele was also increased in asymptomatics when compared with cardiomyopathics (P=0.02; OR=0.35, 95% CI 0.12-0.96). Our data suggest that the CCR5 59029 promoter polymorphism may be involved in a differential susceptibility to chagasic cardiomyopathy.     

Do CCR5 (CCR5Δ32) and TLR3 (RS5743313) gene polymorphisms prevent chronic hepatitis B infection?

Hepatitis B virus (HBV) is still a significant health problem in human. HBV severity or sensitivity of patients may be based on the individual genetic factors significantly. The aim of this study is to investigate the association of CCR5 (CCR5Δ32), TLR3 (rs5743313) functional gene polymorphisms, interferon-gamma (IFN-ɣ) level in HBV infection, which are thought to play an important role in innate and acquired immunity in patients who have undergone HBV seroconversion and those who have chronic hepatitis B disease and receive treatment. One hundred patients who are became naturally immune against HBV infection (HBsAg negative, anti-HBc IgG, and anti-HBs IgG positive), and 100 patients with chronic hepatitis B infection (>6 months HBsAg positive) who are receiving oral antiviral therapy were compared for CCR5Δ32, TLR3 (rs5743313) genotypes and serum IFN-ɣ level. It was found that CCR5Δ32 polymorphism (Wt/Δ32 and Δ32/Δ32) was significantly higher in the chronic hepatitis B group (p = 0.048) but not for TLR3 gene polymorphism. However, serum IFN-ɣ level was significantly higher in the HBV seroconversion group (75 ± 89 ng/ml) than in the chronic hepatitis B group (4.35 ± 17.27 ng/ml) (p < 0.001). In conclusion, a higher CCR5Δ32 allele frequency in patients with chronic hepatitis B might be considered as a marker of progression to chronic hepatitis.     

The role of the CCR5 Δ32 polymorphism in abdominal aortic aneurysms

Background C‐C chemokine receptor 5 (CCR5) is involved in the regulation of the inflammatory response. Abdominal aortic aneurysms (AAA) may arise as the result of a chronic inflammatory process which is influenced by genetic predisposition. The CCR5 gene is associated with a 32 base pair deletion (the Δ32 polymorphism). The aim of this study was to investigate the role of the CCR5 Δ32 polymorphism in the development of AAA. Methods A case–control study was conducted including 285 patients with AAA and 273 control subjects. A blood sample was taken from each individual and DNA was extracted. CCR5 genotype was determined using the polymerase chain reaction (PCR). Flow cytometry was used to investigate the biological activity of the Δ32 polymorphism. Results There was no significant difference between the AAA and the control group in relation to the Δ32 allele frequency (AAA group 10%, control group = 12%, P = 0.82, chi‐squared analysis). Genotype analysis revealed no significant difference between the groups (AAA vs. controls, wild‐type homozygotes = 82% vs. 77%, heterozygotes = 16% vs. 21%, vs. Δ32 homozygotes = 2% and 2%, respectively, P = 0.33, chi‐squared analysis). The polymorphism was shown to be biologically active with the number of Δ32 alleles correlating with cell expression of ccr5 as detected with flow cytometry (P ≤ 0.05). Conclusion This study demonstrates that the ccr5 Δ32 is a biologically active genetic polymorphism; however, there is no association between this polymorphism and AAA.     

CCR5 and CCR5Δ32 in bacterial and parasitic infections: Thinking chemokine receptors outside the HIV box

The CCR5 molecule was reported in 1996 as the main HIV‐1 co‐receptor. In that same year, the CCR5Δ32 genetic variant was described as a strong protective factor against HIV‐1 infection. These findings led to extensive research regarding the CCR5, culminating in critical scientific advances, such as the development of CCR5 inhibitors for the treatment of HIV infection. Recently, the research landscape surrounding CCR5 has begun to change. Different research groups have realized that, since CCR5 has such important effects in the chemokine system, it could also affect other different physiological systems. Therefore, the effect of reduced CCR5 expression due to the presence of the CCR5Δ32 variant began to be further studied. Several studies have investigated the role of CCR5 and the impacts of CCR5Δ32 on autoimmune and inflammatory diseases, various types of cancer, and viral diseases. However, the role of CCR5 in diseases caused by bacteria and parasites is still poorly understood. Therefore, the aim of this article is to review the role of CCR5 and the effects of CCR5Δ32 on bacterial (brucellosis, osteomyelitis, pneumonia, tuberculosis and infection by Chlamydia trachomatis) and parasitic infections (toxoplasmosis, leishmaniasis, Chagas disease and schistosomiasis). Basic information about each of these infections was also addressed. The neglected role of CCR5 in fungal disease and emerging studies regarding the action of CCR5 on regulatory T cells are briefly covered in this review. Considering the “renaissance of CCR5 research,” this article is useful for updating researchers who develop studies involving CCR5 and CCR5Δ32 in different infectious diseases.