Delta32 Allele Research Articles

The CCR5-Delta32 Genetic Polymorphism and HIV-1 Infection Susceptibility: a Meta-analysis.

The CC chemokine receptor 5 (CCR5) is a chemokine receptor which is widely expressed in several immune cells involved in the inflammatory responses. Previous published studies revealed the relation of the CCR5 gene (CCR5-delta32) with the risk of HIV-1 infection, but the results are debatable and inconclusive. Here by meta-analysis, we have systematically evaluated the relation between the CCR5-delta32 polymorphism and the risk of HIV-1 infection. A comprehensive search in PubMed, EMBASE, CNKI, Cochrane Library, and WanFang database was performed up to April 15, 2018. The pooled odds ratio (ORs) along with its 95% credible interval (95%CI) was used to evaluate the relation between the CCR5-delta32 polymorphism and HIV-1 infection risk. The study included 24 case-control studies involving 4,786 HIV-1 infection patients and 6,283 controls. Compared with the wild-type homozygous genotypes, the results showed that the CCR5-delta32 heterozygotes (OR=1.16, 95%CI=1.02-1.32) had an increased susceptibility to HIV-1 and the delta32 homozygous (OR=0.25, 95%CI=0.09-0.68) had significantly reduced the susceptibility to HIV-1 for healthy controls. Moreover, we have found the delta32 allele carriers (OR=0.71, 95%CI=0.54-0.94) had significantly cut down the HIV-1 infection susceptibility when using exposed uninfected (EU) as controls. We also conducted the stratified analysis by ethnicity, and there significant association was detected in Caucasian in delta32 allele carrier genotype. To summarize, our meta-analysis suggests that the CCR5-delta32 homozygous genotype (delta32/delta32) confer possible protection against HIV-1, especially the exposed uninfected groups.

Frequency of the CCR5-delta32 allele in Brazilian populations: A systematic literature review and meta-analysis

The CCR5 is a chemokine receptor widely expressed by several immune cells that are engaged in inflammatory responses. Some populations have individuals exhibiting a 32bp deletion in the CCR5 gene (CCR5-delta32) that produces a truncated non-functional protein not expressed on the cell surface. This polymorphism, known to be associated with susceptibility to infectious and inflammatory diseases, such as osteomyelitis, pre-eclampsia, systemic lupus erythematous, juvenile idiopathic arthritis, rheumatoid arthritis and HIV/AIDS, is more commonly found in European populations with average frequency of 10%. However, it is also possible to observe a significant frequency in other world populations, such as the Brazilian one. We performed a systematic review and meta-analysis of CCR5-delta32 genetic association studies in Brazilian populations throughout the country to estimate the frequency of this polymorphism. We also compared CCR5-delta32 frequencies across Brazilian regions. The systematic literature reviewed studies involving delta32 allele in Brazilian populations published from 1995 to 2015. Among the reviewed literature, 25 studies including 30 Brazilian populations distributed between the North, Northeast, South and Southeast regions were included in our meta-analysis. We observed an overall allelic frequency of 4% (95%-CI, 0.03–0.05), that was considered moderate and, notably, higher than some European populations, such as Cyprus (2.8%), Italy (3%) and Greece (2.4%). Regarding the regional frequency comparisons between North-Northeast (N-NE) and South-Southeast (S-SE) regions, we observed an allelic frequency of 3% (95%-CI, 0.02–0.04) and 4% (95%-CI, 0.03–0.05), respectively. The populations from S-SE regions had a slightly higher CCR5-delta32 frequency than N-NE regions (OR=1.41, p=0.002). Although there are several studies about the CCR5-delta32 polymorphism and its effect on the immune response of some infectious diseases, this report is the first meta-analysis study that provides a descriptive study of the distribution of CCR5-delta32 allele in Brazilian population.

Protective Effect of CCR5 Delta-32 Allele Against HIV-1 in Mexican Women

C-C chemokine receptor type 5 (CCR5) is known for its role as a co-receptor for HIV-1 infection. Some individuals possess a 32 bp deletion, known as Delta-32 allele which has been reported to confer resistance to HIV-1 infection. In order to estimate the distribution of Delta-32 allele of CCR5 gene, 1034 mestizo individuals from the Northwest of Mexico, including 385 HIV-1-infected individuals, 472 healthy controls and 177 uninfected female sex workers; were examined by allele-specific PCR. There was no statistically significant difference in the frequency of Delta-32 allele between HIV-1 positive and healthy individuals (OR= 1.1, p= 0.6). However, we found a significantly reduced prevalence of CCR5 Delta-32 heterozygous genotype in female patients (OR= 0.084, 95% CI= 0.011 - 0.630, p= 0.002), as well as in allele frequency, compared to male patients. Furthermore, we observed an inverse relationship between allele frequency and the risk of HIV-1 transmission and AIDS progression among female healthy controls, sex workers and HIV-1 infected groups. Our findings support previous data showing Delta-32 as a genetic protective factor against HIV-1 infection in Mexican women, as well as in women from other populations.

Single Cord Blood Transplantation Combined With An HLA Mismatched Third Party Donor For High-Risk Hematological Patients With HIV Infection

BackgroundThe safety and usefulness of unrelated umbilical cord blood (CB) stem cell transplantation (SCT) in patients candidates for allogeneic SCT and HIV infection is unknown. Single CB with the co-infusion of CD34+ cells from a third party HLA-mismatched donor (TPD), or Haplo-cord SCT, has shown to reduce the period of post-transplant neutropenia and related early complications associated with single CB transplantation. This platform could potentially reduce the risk of early infections in this particular group of patients. On the other hand, the use of a cell source homozygous for the CCR5 delta32 allele mutation, which confers high resistance against HIV-1 acquisition, is of particular interest in HIV+ patients. Methods and ResultsWe report here on the first two patients with HIV infection and high-risk haematological malignancies who underwent haplo-cord SCT in two different centers: (Case 1) a 53 year-old male patient with high-risk MDS; (Case 2) a 34 year-old male with Burkitt lymphoma in CR2. Both CB transplants were performed using the haplo-cord platform with the co-infusion of mobilized and selected CD34+ cells from a TPD. Conditioning regimen were myeloablative in both cases. Case 1 had the additional potential benefit from the use of a CB unit with the homozygous CCR5delta32 mutation. Both cases achieved neutrophil and platelet engraftment similarly to previous haplo-cord SCT performed in HIV negative patients, as well as full CB chimerism. However, case 1 developed beside a severe lung infection, relapse of the underlying malignancy 2 months after SCT and died consequently. Case 2 presented one episode of bacterial sepsis with good response to antibiotics, and one episode of CMV reactivation controlled with valgancyclovir. Thirteen months after SCT, this patient is alive and in CR. Extensive analyses of viral and immunological compartments were performed showing the early viral dynamics in both patients. ConclusionsCB SCT is feasible in patients eligible for allogeneic SCT and HIV infection. The haplo-cord strategy with the co-infusion of auxiliary cells from a TPD seems to offer a fast neutrophil engraftment similarly to HIV negative patients. Therefore, this strategy should be considered in patients with HIV infection and indication for allogeneic SCT, whenever CB is the source of choice and especially if a CCR5 mutated unit is available. Disclosures:Kuball:Miltenyi: GMP product development Other.

Investigation of the frequency of the mutant CCR5-Δ32 allele related to HIV resistance in Turkey

To determine the frequency with which the CCR5-\Delta32 mutant allele caused resistance to HIV, which is main agent of AIDS in all geographic regions of Turkey. Materials and methods: Randomly selected human blood samples from 400 healthy individuals were collected. The polymerase chain reaction method was used to determine the CCR5-\Delta32 polymorphism and samples were screened using 2 primers. Results: The frequency of wild alleles was found to be 0.9738 and the frequency of mutant alleles was found to be 0.0262. The highest frequency of the CCR5-\Delta32 allele was found to be 0.0726 in the Central Anatolia region. The lowest frequency of the CCR5-\Delta32 allele was found to be 0.0093 in the Southeast Anatolia and the Mediterranean regions. The mutant allele was not observed in any individuals from the Marmara region. Homozygosity was not observed in terms of this mutant allele in the individuals studied. Conclusion: According to the data obtained from this study, the frequency of CCR5-\Delta32, except for in the Marmara region, showed parallelism with a decrease consistent with a north-south direction across the world. This study was conducted to determine the frequency of the CCR5-\Delta32 allele, which is important for the evaluation of samples that are representative of all the geographic regions of Turkey.

Common CCR 5 Polymorphism in Stroke The CCR 5 Δ32 Polymorphism Differentiates Cardioembolism from Other Aetiologies of Ischaemic Cerebrovascular Diseases

Inflammation is involved in the development of atherosclerosis. The CC chemokine receptor 5 (CCR5) initiates chemotaxis and modulates the inflammation secondary to atherosclerosis and related vascular diseases. The CCR5 Delta32 polymorphism influences the expression of CCR5 on the cell surface. The purpose of this study was to examine the effect of the Delta32 polymorphism in ischaemic cerebrovascular disease (ICVD). The CCR5 Delta32 polymorphism was genotyped in 1462 individuals: 562 ischaemic stroke (IS), 97 transient ischaemic attack (TIA) and in 803 healthy controls. All 659 ICVD patients were categorized according to the Trial of Org 10172 in Acute Stroke Treatment aetiological classification. The investigated subtypes were large artery atherosclerosis (LAA), cardioembolism (CE), small artery occlusion (SAO) and cryptogenic disease (CRYPT). Genotyping was performed with the TaqMan polymerase chain reaction. The Delta32 allele was less frequent in CE patients compared with LAA (OR, 0.4; 95% CI, 0.24-0.79; P = 0.008), SAO (OR, 0.5; 95% CI, 0.29-0.84; P = 0.01), CRYPT (OR, 0.5; 95% CI, 0.28-0.82; P = 0.008) and controls (OR, 0.5; 95% CI, 0.36-0.82; P = 0.002). Multiple logistic regression analysis showed that the Delta32 allele is associated with a lower risk for cardioembolic ICVD (OR 0.5; 95% CI, 0.28-0.75; P = 0.002) when compared with ICVD of other causes. The Delta32 polymorphism of CCR5 may differentiate cardioembolism from the remaining causes of ICVD.

Sequence variants of chemokine receptor genes and susceptibility to HIV-1 infection.

Genetic susceptibility to HIV infection was previously proven to be influenced by some chemokine receptor polymorphisms clustering on chromosome 3p21. Here the influence of 5 genetic variants was studied: Delta32 CCR5, G(-2459)A CCR5, G190A CCR2, G744A CX3CR1 and C838T CX3CR1. They were screened in a cohort of 168 HIV-1 positive adults [HIV(+) group] and 151 newborns [control group] from northwestern Poland. PCR-RFLP was performed to screen for the variants (except for Delta32 CCR5 polymorphism, where PCR fragment size was sufficient to identify the alleles) and then electrophoresed on agarose gel to determine fragment size. Distribution of genotypes and alleles was not significantly different between the groups except for the CCR5 polymorphisms, with the Delta32 allele and the (-2459)A CCR5 allele more frequent among neonates than in the HIV(+) group. No Delta32/Delta32 homozygotes were found in the HIV(+) group, but 16.1 percent were Delta32/wt heterozygotes. In the control group, 1.3 percent; were Delta32/Delta32 homozygotes and 26.0percent were Delta32/wt heterozygotes. Linkage between the chemokine polymorphisms was calculated using the most informative loci for haplotype reconstruction. Haplotypes containing Delta32 CCR5, 190G CCR2 and 744A CX3CR1 were found to be significantly more common in the control group. This suggests an association between these haplotypes and resistance to HIV-1 infection.

Association of chemokines receptor (CCR5 Δ32) in idiopathic recurrent miscarriages among north Indians

Human reproduction is a complex process involving multiple factors for the success of pregnancy. Chemokines are one of the immunomodulators which may determine pregnancy outcome. In the present study, we have tested genetic association between CCR5 Delta32 polymorphism and idiopathic recurrent miscarriages (IRM) among north Indians. Two hundred patients and 300 age, sex and ethnically matched controls were genotyped for CCR5 Delta32 polymorphism, genotype and allele frequencies were compared in both the groups. IRM patients had a three times higher (5.5 vs. 1.7%) frequency of heterozygote genotype (P = 0.0335, OR = 3.43; 95% CI = 1.17-10.04). Allele frequency in IRM patients was 3.7 and 0.83% among controls and the differences were statistically significant (P = 0.0349, OR = 3.37; 95% CI = 1.16-9.76). Our results demonstrated that it had a higher frequency of CCR5 Delta32 at allelic level suggesting a possible susceptibility trend (OR = 3.43) and CCR5 Delta32 may be a potential genetic risk factor for IRM.

CCR5 Δ32 Polymorphism: Associated with Gallbladder Cancer Susceptibility

Inflammation of gallbladder is an established risk factor for gallbladder cancer (GBC) pathogenesis. Chemokine receptors play crucial role in antitumour immunity and are involved in inflammation and pathogenesis of cancers. Present study was aimed to examine the role of CCR5 Delta32 polymorphism in conferring genetic susceptibility to GBC. Present case-control study included 144 proven GBC patients and 210 healthy controls. Genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Statistically significant difference was observed in distribution of CCR5+/Delta32 genotype (P = 0.028) [odds ratio (OR) = 2.850; 95% confidence interval (CI) = 1.1-7.2] and CCR5 Delta32 allele (P = 0.012) (OR = 3.145, 95% CI = 1.2-7.7) in GBC patients which was conferring high risk. Stratification of GBC patients showed significant association of CCR5+/Delta32 genotype and CCR5 Delta32 allele with GBC patients with and without gallstones. Analysis based on age of onset and gender suggested significant association of CCR5 Delta32 allele with early onset (<50 years) of the disease but only marginal influence of gender in CCR5 Delta32-mediated risk of cancer. Risk was further modulated by tobacco usage and significantly increased risk was observed in tobacco users with CCR5+/Delta32 genotype. In conclusion, CCR5+/Delta32 genotype and CCR5 Delta32 allele confer significant risk for GBC particularly in patients with early onset and tobacco usage. Role of CCR5+/Delta32 polymorphism in GBC susceptibility is independent of gallstone formation.

Analysis of the CC chemokine receptor 5 delta32 polymorphism in a Brazilian population with cutaneous leishmaniasis

Patients with mucocutaneous leishmaniasis (MCL) show a vigorous T-cell immune response against Leishmania braziliensis. Because the Th response is associated with inflammation, the non-functional CC chemokine receptor 5 (CCR5) may rely in a less severe inflammatory state. The aim of this study was to investigate the CCR5 gene in a Brazilian population with leishmaniasis compared with healthy control subjects and to determine the progression from cutaneous to MCL in the Delta32 allele carriers. Among 100 patients with Montenegro skin test and indirect immunofluorescence assay (IIF) values positive for leishmaniasis, there were 32% women and 68% men. The patients were 89% CCR5/CCR5, 10% CCR5/Delta32, and 1% Delta32/Delta32, while healthy subjects showed a 91% incidence of CCR5/CCR5, 8% of CCR5/Delta32, and 1% of Delta32/Delta32. The CCR5/CCR5 patients (89%) showed a large spectrum of clinical manifestations, where 22.47% had active mucous lesions and 77.53% had cutaneous lesions. In this work, the Delta32 allele carriers (10%) showed only cutaneous manifestations when compared with wild-type individuals. Finally, with regard to the Delta32 allele carriers, a less severe spectrum of clinical manifestations was observed in comparison with wild-type individuals. Although a lack of mucocutaneous lesions was evident among Delta32 allele carriers, the number of individuals studied was small. Therefore, further investigations are needed to elucidate the role of CCR5 in the clinical aspects of leishmaniasis.

The 32‐base pair deletion of the chemokine receptor 5 gene (CCR5‐Δ32) is not associated with primary sclerosing cholangitis in 363 Scandinavian patients

CCR5 is a chemokine receptor expressed on T-cells and macrophages. A 32-base pair deletion in the chemokine receptor 5 gene (CCR5-Delta32) leads to a non-functional receptor. Conflicting evidence exists whether this deletion is associated with primary sclerosing cholangitis (PSC). We genotyped the CCR5-Delta32 variant in 363 PSC patients and 366 controls. No significant increase in the Delta32 allele frequency was detected in the PSC patients compared to controls (12.7% vs 10.7% OR = 1.22, 95% CI [0.88, 1.68], P = 0.23). Survival analysis did not reveal any significant effects from CCR5-Delta32 genotypes on disease progression. Thus, in this study (power > 90%, given OR = 2, alpha = 0.05), we were unable to replicate previous findings and our results do not support an involvement of CCR5-Delta32 in either PSC susceptibility or progression.

The Geographic Spread of the CCR5 Δ32 HIV-Resistance Allele

The Δ32 mutation at the CCR5 locus is a well-studied example of natural selection acting in humans. The mutation is found principally in Europe and western Asia, with higher frequencies generally in the north. Homozygous carriers of the Δ32 mutation are resistant to HIV-1 infection because the mutation prevents functional expression of the CCR5 chemokine receptor normally used by HIV-1 to enter CD4+ T cells. HIV has emerged only recently, but population genetic data strongly suggest Δ32 has been under intense selection for much of its evolutionary history. To understand how selection and dispersal have interacted during the history of the Δ32 allele, we implemented a spatially explicit model of the spread of Δ32. The model includes the effects of sampling, which we show can give rise to local peaks in observed allele frequencies. In addition, we show that with modest gradients in selection intensity, the origin of the Δ32 allele may be relatively far from the current areas of highest allele frequency. The geographic distribution of the Δ32 allele is consistent with previous reports of a strong selective advantage (>10%) for Δ32 carriers and of dispersal over relatively long distances (>100 km/generation). When selection is assumed to be uniform across Europe and western Asia, we find support for a northern European origin and long-range dispersal consistent with the Viking-mediated dispersal of Δ32 proposed by G. Lucotte and G. Mercier. However, when we allow for gradients in selection intensity, we estimate the origin to be outside of northern Europe and selection intensities to be strongest in the northwest. Our results describe the evolutionary history of the Δ32 allele and establish a general methodology for studying the geographic distribution of selected alleles.

Distribution of the mutated Δ32 allele of the CCR5 gene in a Sicilian population

The CCR5 gene encodes a cell-surface chemokine receptor molecule that serves as a co-receptor for macrophage-tropic strains of human immunodeficiency virus type 1 (HIV-1). A mutation in this gene may alter the expression or the function of the protein product, thereby altering chemokine binding and/or signalling or HIV-1 infection of cells that normally express CCR5 protein. Individuals homozygous for a 32-bp deletion allele of CCR5 (CCR5 delta32), heritable as a Mendelian trait, are relatively resistant to HIV-1 infection. The CCR5 delta32 mutation is present in the Caucasian population at different frequencies. The aim of this study was to investigate the frequency of truncated alleles of the CCR5 delta32 gene in a Sicilian population, as the interpopulation variation in CCR5 delta32 frequency may be a significant factor in the prediction of AIDS endemicity in future studies. We examined 901 healthy individuals from several Sicilian provinces. We found a mean (+/- standard deviation) delta32 allele frequency (fr) of 0.04 +/- 0.012. The highest value was observed in the province of Messina, with a mean delta32 allele frequency of 0.06 +/- 0.024, where we collected samples from a cohort of 114 HIV-1-infected individuals. The observed frequency amongst these patients was quite low (fr = 0.03 +/- 0.031) compared to the healthy population, although the difference was not statistically significant.

Is Spatial Distribution of the HIV-1-resistant CCR5Δ32 Allele Formed by Ecological Factors?

It has been proposed that the Delta32 mutation in the chemokine receptor gene, inducing resistance to HIV-1 and, probably, to other virus infections, has undergone selection in historical times. The frequency of this mutant allele has changed rapidly both in time (during the last two millennia) and in space (across Eurasia). We compiled a global database on Delta32 allele frequencies in 300 populations. Nearly 10 percent of them are our data on 35 East European populations analyzed here for the first time. A detailed map of Delta32 frequency distribution was constructed and statistically analysed. We found a linearly decreasing trend with a maximum in areas surrounding the Baltic and White seas. Significant correlations with ground surface temperature were revealed. However, compared with our previous results, these correlations diminished, indicating that the influence of climate on Delta32 distribution was, if anything at all, indirect. The proposed scenario includes: i) arise and initial spread of the mutation among Uralic-speaking populations; ii) a frequency increase in northeastern Europe as a result of selection and/or genetic drift; iii) secondary spread (with selection continued) due to gene flow and the migrations of northern Europeans across the globe.

Further support for the association of CCR5 allelic variants with asthma susceptibility.

English and German nuclear families containing multiple asthmatic children and asthmatic parents were analysed to retest a recently reported association between resistance to asthma and the delta32 allele of chemokine receptor 5 (CCR5). Analysis of the families by the transmission-disequilibrium test (TDT) revealed a non-significant trend in the English families that provided marginal confirmation of the association (P < 0.125), but no similar trend was observed in the German families. Case-control comparison of delta32 allele and genotype frequencies in asthmatic vs. non-asthmatic parents revealed a significantly lower frequency of delta32 in asthmatic English parents (P < 0.009) and a similar but non-significant trend in German parents (P < 0.265). Taken together, the pattern of results provides confirmation for the previously observed delta32-asthma association and indicates that susceptibility to asthma may be influenced by CCR5 or another gene in chromosomal region 3p21.

Antibodies to varicella-zoster virus in blood donors with genetic variance in CC chemokine receptor 5

Carriers of a 32 bp deletion (Delta32) allele of the CC chemokine receptor 5 (CCR5) gene are reported to be more likely to lack antibodies to varicella-zoster virus than CCR5 wild-type individuals. To find out whether CCR5-Delta32 is associated with the seroprevalence of varicella-zoster virus infection, we tested blood donors with different CCR5-Delta32 genotypes for varicella-zoster virus IgG. Antibody to varicella-zoster virus was present in 209 (99.5%) of 210 CCR5-Delta32 carriers and exactly the same proportion of CCR5 wild-type individuals (209 of 210). We have therefore found no evidence that the CCR5-Delta32 allele is associated with decreased seroprevalence of varicella-zoster virus infection.

Distribution of Δ32 alelle of the CCR5 gene in the population of Poland

The chemokine receptor CCR5 constitutes a major co-receptor for the R5 strains of HIV-1, and a mutant allele of the CCR5 gene, especially in the homozygous form delta32/delta32, confers resistance against infection by the virus. The frequency of the delta32 allele was determined in blood donors from 16 provinces, covering the entire territory of Poland. Among 861 individuals 182 (21.1%) were carriers of the mutated allele: 7 of them (0.8 %) were homozygotes delta32/delta32, and 175 (20.3%) were heterozygotes +/delta32, resulting in a 10.9% frequency of the delta32 allele. The highest frequencies of the mutated allele were found in the eastern and western provinces, and the lowest frequencies of the delta32 allele were detected in the provinces in the center of the country. This pattern of distribution may reflect the migration of the population from the eastern territories of Poland to the western part of the country after World War II.

The frequency of mutation in CCR5 gene among Koreans.

To better understand a role of the delta32 allele of the CCR5 gene in HIV-1 transmission and disease progression, we determined the CCR5 genotypes within several groups of Koreans. Amplification of DNA from each subject was achieved with polymerase chain reaction, using the CCR5 specific primer pair, which flanks the 32 bp deletion. The 1.2 kb coding sequences of CCR5 were examined to see the possible effects of CCR5 polymorphism. All of the 339 healthy, HIV-uninfected individuals had no mutation in the CCR5 gene. All of the 115 HIV-1-infected patients including 11 long-term non-progressors (LTNPs) and 18 discordant spouses were also wild homozygotes. No variation in the 1.2kb CCR5 coding sequence was found in 5 LTNPs and 5 discordant spouses. In conclusion, the 32 bp deletion mutant is rarely present in Koreans. Our data suggest that factors other than the CCR5 coding sequences may also play a role in the resistance to HIV infection.

The CC-chemokine receptor 5 (CCR5) is a marker of, but not essential for the development of human Th1 cells.

The CC-chemokine receptor 5 (CCR5) has recently been described as a surface marker of human T cells producing type 1 (Th1) cytokines. Here we confirm that CCR5 is expressed on human Th1 but not on Th2 T-cell clones. Using intracellular cytokine staining, we show that alloantigen specific CD4+ T-cell lines derived from a CCR5-deficient individual (delta32 allele homozygote) contain high numbers of both interferon gamma (IFN-gamma) and interleukin (IL)-2 producing cells, low numbers of IL-10 producing cells and no IL4 or IL-5 producing cells when stimulated with phorbol ester and ionomycin in vitro. These results were similar to those obtained from alloantigen specific CD4+ T-cell lines derived from CCR5 expressing individuals. An enzyme-linked immunoabsorbent assay (ELISA) confirmed that the Th1 cytokine-positive cells from the CCR5-deficient individual were able to produce equal amounts of cytokines when compared to T-cell lines from CCR5-expressing individuals, These results demonstrate that CCR5-negative T cells display the same capacity of Th1 T-cell differentiation as T cells derived from CCR5-expressing individuals. Thus, CCR5 expression is not essential for differentiation of human Th1 T cells.

Frequency of a Mutated CCR-5 Allele (Delta32) among Italian Healthy Donors and Individuals at Risk of Parenteral HIV Infection

The aim of this study was to assess the frequency of a truncated allele of the CCR-5 gene (delta32) in Italy, and address its possible role in parenteral HIV transmission, as well as its influence in HIV-associated disease progression. In 371 unrelated seronegative healthy blood donors the delta32 allele frequency was 0.047; this figure was significantly different from those reported in northern America and northern Europe populations. However, delta32 allele frequency in healthy individuals did not differ significantly from that found in 54 seronegative drug users (0.065), 98 seronegative hemophiliacs (0.051), and 81 seropositive hemophiliacs (0.049). Although in seropositive hemophiliacs the wt/delta32 heterozygous genotype was associated with a trend to a slower decline in CD4+ cell counts, its presence did not seem to influence disease progression, as comparable delta32 allele frequency frequencies were found among progressing (0.042) and nonprogressing (0.111) patients. These data do not seem to support a protective role of the delta32 allele in preventing HIV infection through the parenteral route, or in influencing the natural history of the disease in this particular risk category, although the delta32 heterozygous state was associated with lower plasma viremia levels. On the other hand, the finding of non-syncytium-inducing HIV strains in the majority of delta32 heterozygous seropositive patients suggests that its presence could not be a major factor in driving a switch toward more cytopathic, T-tropic HIV strains through selective pressure in coreceptor usage.