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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies on screening genes conferring resistance to HIV-1 and AIDS onset have shown a direct relationship between a 32 base pair (bp) deletion in the CCR5 beta-chemokine receptor gene (delta ccr5 mutant allele) and long survival of HIV-1 infected individuals bearing this mutation. These findings led to an interest in studies of delta ccr5 allele distribution in human populations. In the present study, polymerase chain reactions (PCR) in genomic DNA samples, using specific CCR5 oligonucleotide primers surrounding the breakpoint deletion, detected a 193-bp product from the normal CCR5 allele and a 161-bp product from the 32-bp deletion allele. In an investigation of the urban Brazilian population we detected a 93% frequency of normal CCR5/CCR5 homozygous individuals and a 7% frequency of CCR5/delta ccr5 heterozygous individuals. The frequency of the delta ccr5 mutant allele in this population is 0.035; however, no homozygous delta ccr5 individual has been detected thus far. This is the first evidence for the contribution of the delta ccr5 allele to the genetic background of the urban Brazilian population, which is characterized by intense ethnic admixture. These findings open perspectives for further studies on the relationship between delta ccr5 allele frequency and AIDS onset in high-risk HIV-1 exposures individuals.
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PMID:Frequency of the delta ccr5 deletion allele in the urban Brazilian population. 965 77

Chemokine receptors play a crucial role in the recruitment of immune cells to sites of inflammation. Although chronic diseases of the brain are often accompanied by inflammatory events, there is presently no information about the occurrence and regulation of these receptors in the central nervous system (CNS). Moreover, one CC-chemokine receptor, CKR5, has recently been identified as coreceptor for HIV-1 entry into macrophages. HIV-1 target cells in brain are macrophage-related microglia, which suggests that they are infected by the same mechanism (He et al.,: Nature 385:645-649, 1997). Although rats are not susceptible to HIV-1 infection, they can be used to study chemokine receptor regulation in a variety of brain pathologies. After cloning CC-CKR5 and establishing reverse transcriptase polymerase chain reaction (RT-PCR) for its ligands macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and regulated on activation, normal T cell-expressed and secreted (RANTES), we studied expression of these four mRNAs in purified microglia and compared it with their expression in rat brain. Lipopolysaccharide (LPS)-treated microglia showed transiently increased mRNA levels of both CKR5 and its ligands. Similar data were obtained from brains of LPS-injected rats. In middle cerebral artery occluded (MCAO)-animals, RANTES mRNA was unaffected, whereas CKR5 mRNA showed a sustained rise until 96 hr after surgery. MIPs exogenously added to microglial cultures markedly reduced CKR5 mRNA expression, whereas RANTES did not. MIP mRNAs, in contrast to RANTES and CKR5 mRNAs, were undetectable in normal brain. RANTES appears to play a role distinct from MIPs in brain. In summary, upregulation of CC-chemokines and CKR5 in the CNS upon bacterial infection or in ischemia may impact on microglial activation stage and result in increased risk of HIV-1 infection.
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PMID:Cloning of rat HIV-1-chemokine coreceptor CKR5 from microglia and upregulation of its mRNA in ischemic and endotoxinemic rat brain. 967 Sep 89

32-bp inactivating deletion in the beta-chemokine receptor 5 (CCR5) gene, common in Nothern European populations, is associated with reduced HIV-1 transmission risk and delayed disease progression. We have studied the deletion distribution in many populations in Eurasia by polymerase chain reaction analysis of 531 DNA samples representing West and East Siberian, Central Asian, and Far Eastern parts of Russia. An unusually high frequency (11.1%) of the deleted variant in natives of West Siberia, of Finno-Ugrian descent, was observed. Furthermore, the deletion was infrequent in indigenous populations of Central Asia, East Siberia, the Russian Far East, and Canada. We conclude that the delta(ccr5) distribution is limited primarily to Europeans and related western Siberian Finno-Ugrian populations, with a sharp negative gradient toward the east along the territory of Russian Asia.
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PMID:Distribution of CCR5-delta 32 gene deletion across the Russian part of Eurasia. 970 33

The CCR5 gene encodes one of the major human immunodeficiency virus type 1 (HIV-1) coreceptors. A 32-bp deletion in this gene (delta ccr5) is associated with relative resistance to disease progression in heterozygous HIV-1-infected persons. The effect of this mutation on virologic and immunologic parameters was determined in a cohort of 45 perinatally HIV-1-infected children prospectively followed after 5 years of age. At a median age of 8.3 years, heterozygous children had significantly lower virus load than homozygous children (median, 3.3 vs. 4.1 log copies/mL, P < .009) and higher percentages of CD4 T cells (median, 26% vs. 17%, P < .07). However, there was no discernible influence of the CCR5 genotype on the percentages of CD8 T cells (P < .27) or on HIV-specific cytotoxic T lymphocyte activities (P < .65). There was a trend for lower rates of progression to AIDS (CDC stage C) in heterozygous children. These data confirm a major role for the CCR5 coreceptor in HIV-1 pathogenesis in children.
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PMID:Impact of heterozygosity for the chemokine receptor CCR5 32-bp-deleted allele on plasma virus load and CD4 T lymphocytes in perinatally human immunodeficiency virus-infected children at 8 years of age. 980 29

The chemokine receptor 5 (CCR5) serves as a fusion cofactor for macrophage-tropic strains of HIV-1. In addition, CCR5 has been shown to mediate the entry of poxviruses into target cells. Individuals homozygous for the Delta32 deletion-mutation have no surface expression of CCR5 and are highly protected against HIV-1 infection. To gain insights into the evolution of the mutation in modern populations, the relatively high frequency of the Delta32-ccr5 allele in some European and Jewish populations is explored here by examining haplotypes of 3p21.3 constructed of five polymorphic marker loci surrounding CCR5. By sampling Ashkenazi, non-Ashkenazi and non-Jewish populations, we utilize the natural experiment that occurred as a consequence of the Jewish Diaspora, and demonstrate that a single mutation was responsible for all copies of Delta32. This mutation must have moved from Northern European populations to the Ashkenazi Jews where evidence suggests that Delta32 carriers of both groups were favored by repeated occurrence of epidemic small pox beginning in the 8th century AD.
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PMID:Evolution of the CCR5 Delta32 mutation based on haplotype variation in Jewish and Northern European population samples. 1133 78

Mycobacterium tuberculosis (MTB) and human immunodeficiency virus type 1 (HIV-1) are virulent intracellular pathogens that enter and replicate within macrophages, which represent their reservoire. Public health problems are greatly compounded when the two diseases co-exist, and this is the reason why Acquired Immunodeficiency Syndrome (AIDS) and tuberculosis (TB) have been termed "the cursed duet", given the synergistic effect they exert one each other. With the depression of immunity caused by HIV-1 infection, latent MTB infection is much more likely to progress to clinically significant disease. On the other hand, TB results in activation of T cells and macrophages that may harbor latent HIV. Here some data are reviewed that can contribute to clarify the mechanisms involved in the concurrent infection, given that MTB infection has been shown to be able to: a) enhance HIV-1 replication in macrophages, b) augment CC-CKR5 (CCR5) expression on macrophage membrane, and, c) induce apoptosis in a portion of infected macrophages.
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PMID:Monocytes/macrophages in HIV infection and tuberculosis. 1169 39

Recent epidemiological data and projections indicate that HIV infection will spread rapidly in India. An allele Delta ccr5 of the beta-chemokine receptor gene CCR5 has been found to confer protection against HIV-1. We find that this protective allele is absent in most ethnic populations of India, except some populations of the northern and western regions where this allele may have been introduced by Caucasian gene flow. The implications of this finding are discussed in the light of increasing HIV prevalence in India.
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PMID:Absence of the HIV-1 protective Delta ccr5 allele in most ethnic populations of India. 1178 92

Opportunistic infections such as pulmonary tuberculosis (TB) increase local HIV-1 replication and mutation. As AIDS progresses, alteration of the HIV-1 gp120 V3 sequence is associated with a shift in viral coreceptor use from CCR5 (CD195) to CXCR4 (CD184). To better understand the effect of HIV/TB coinfection, we screened transcripts from bronchoalveolar lavage cells with high density cDNA arrays and found that CXCR4 mRNA is increased in patients with TB. Surprisingly, CXCR4 was predominately expressed on alveolar macrophages (AM). Mycobacterium tuberculosis infection of macrophages in vitro increased CXCR4 surface expression, whereas amelioration of disease reduced CXCR4 expression in vivo. Bronchoalveolar lavage fluid from TB patients had elevated levels of CCL4 (macrophage inflammatory protein-1beta), CCL5 (RANTES), and CX3CL1 (fractalkine), but not CXCL12 (stromal-derived factor-1alpha). We found that M. tuberculosis infection of macrophages in vitro increased viral entry and RT of CXCR4-using [corrected] HIV-1, but not of CCR5-using [corrected] HIV-1. Lastly, HIV-1 derived from the lung contains CD14, suggesting that they were produced in AM. Our results demonstrate that TB produces a permissive environment for replication of CXCR4-using virus by increasing CXCR4 expression in AM and for suppression of CCR5-using HIV-1 by increasing CC chemokine expression. These changes explain in part why TB accelerates the course of AIDS. CXCR4 inhibitors are a rational therapeutic approach in HIV/TB coinfection.
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PMID:Mycobacterium tuberculosis-induced CXCR4 and chemokine expression leads to preferential X4 HIV-1 replication in human macrophages. 1512 13

The CC chemokine receptor 5 (CCR5) gene of primates encodes a transmembrane protein involved in cellular signaling of some cell types of the immune system. Numerous studies have shown that this peptide is used by lentiviruses in conjunction with the CD4 receptor to mediate binding and entry in target cells of human and non-human primates. New World monkeys (NWM), differently from their African counterparts, have no description of in natura lentivirus infection. Some evidences suggest that a blockage occurs at the viral entry step of infection. To investigate this possibility, we have cloned and sequenced CCR5 genes from several representatives of Platyrrhini, and compared their sequences with those of other Platyrrhini and Catarrhini species available at public databases. Platyrrhini CCR5 genes were shown to be more genetically diverse than their Catarrhini correlates, and their phylogenetic relationships based on that locus were in agreement with previous studies. Comparison of Platyrrhini and Catarrhini CCR5 consensus sequences evidenced several amino acid residues that differ between both groups, some of which have been experimentally associated with lentiviral interaction. A codon-based positive selection analysis showed that some of these sites seem to be under strong selection for variation among the Platyrrhini but not among Catarrhini species. These results suggest the potential involvement of those sites in the apparent refraction of some NWM to lentiviruses. The high ccr5 genetic diversity observed in Platyrrhini, however, argues for a more extensive infection analysis of diverse NWM species to evaluate this resistance and the potential use of those primates as HIV/AIDS animal models.
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PMID:CCR5 chemokine receptor gene evolution in New World monkeys (Platyrrhini, Primates): implication on resistance to lentiviruses. 1573 19

CCR5 is a seven-transmembrane G-protein-coupled receptor that binds the CC-chemokines including RANTES, eotaxin, MIP-1alpha and beta. CCR5 serves as an essential coreceptor for cell entry of R5 (macrophage-tropic, nonsyncytium-inducing) strains of HIV-1. To date, four deletions have been found in human and primate ccr5. There is little evidence, however, on how these deletion mutations occur. In the present study, we analyzed ccr5 sequences of both mutants and wild type and found that direct repeats flanked the breakpoints of the deletions, suggesting that these deletions resulted from slipped mispairing during DNA replication. Of particular interest was the location of these deletions in or near the regions with higher negative FORS-D values. High negative FORS-D values stand for high stem-loop potential determined by base order and influence mainly the formation of stem-loop structures. Therefore, the particular location of these deletions suggests that the local sequence of bases might be important in the initiation of deletions mediated by DNA slip replication in concert with direct repeats.
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PMID:Local base order influences the origin of ccr5 deletions mediated by DNA slip replication. 1614


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