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

The effects of chemokine and chemokine receptor genetic polymorphisms such as stromal derived factor 1 (SDF1-3'A), CCR2-64I, and CCR5-delta32 associated with HIV-1 transmission and/or rate of disease progression in infected study subjects remain highly controversial and have been analyzed primarily only in adults. We have investigated whether these polymorphisms may provide similar beneficial effects in children exposed to HIV-1 perinatally. The prevalence of CCR2-64I allele was significantly increased (p = .03) and the CCR2-64I genotype distribution was not in Hardy-Weinberg equilibrium, among HIV-1-exposed uninfected infants. Moreover, in the HIV-1-infected group, a delay to AIDS progression was observed among carriers of CCR2-64I allele. This is the first report that suggests a protective role of CCR2-64I allele in mother-to-infant HIV-1 transmission and documents a delay in disease progression, after the child has been infected with HIV-1. However, SDFI-3'A and CCR5-delta32 alleles did not modify the rate of HIV-1 transmission or disease progression in HIV-1-infected children.
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PMID:Protective effect of CCR2-64I and not of CCR5-delta32 and SDF1-3'A in pediatric HIV-1 infection. 1070 56

The host and viral factors that underlie infection with HIV-1 vary considerably with some individuals progressing to AIDS within 3 to 5 years after infection, whereas others remain clinically asymptomatic for over 10 years. Host factors that may contribute to disease progression include HLA and allelic variants of the chemokine receptors CCR5 and CCR2, which have been shown to influence both long-term survival and rapid progression. In this study, we have examined the contribution of HLA and polymorphisms in CCR5 and CCR2 to long-term survival in transfusion-acquired HIV-1-infected individuals. We have found a higher number of HLA-A32 and -A25 alleles but a lower number of the HLA-B8 allele in the study group compared with the frequencies seen in the HIV-1-negative Australian caucasian population. However, there was no apparent contribution by allelic variants of CCR5 and CCR2 to long-term survival and the combined influence of HLA and CCR polymorphisms could not be evaluated in this relatively small (n = 20) group of study subjects. The results of this work support a role for HLA in long-term nonprogression though the presence in the Sydney Blood bank Cohort of nef-defective HIV-1 may confound associations between certain HLA alleles and long-term survival in the face of infection with HIV-1.
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PMID:HLA and other host factors in transfusion-acquired HIV-1 infection. 1071 11

Factors accounting for long-term nonprogression may include infection with an attenuated strain of human immunodeficiency virus type 1 (HIV-1), genetic polymorphisms in the host, and virus-specific immune responses. In this study, we examined eight individuals with nonprogressing or slowly progressing HIV-1 infection, none of whom were homozygous for host-specific polymorphisms (CCR5-Delta32, CCR2-64I, and SDF-1-3'A) which have been associated with slower disease progression. HIV-1 was recovered from seven of the eight, and recovered virus was used for sequencing the full-length HIV-1 genome; full-length HIV-1 genome sequences from the eighth were determined following amplification of viral sequences directly from peripheral blood mononuclear cells (PBMC). Longitudinal studies of one individual with HIV-1 that consistently exhibited a slow/low growth phenotype revealed a single amino acid deletion in a conserved region of the gp41 transmembrane protein that was not seen in any of 131 envelope sequences in the Los Alamos HIV-1 sequence database. Genetic analysis also revealed that five of the eight individuals harbored HIV-1 with unusual 1- or 2-amino-acid deletions in the Gag sequence compared to subgroup B Gag consensus sequences. These deletions in Gag have either never been observed previously or are extremely rare in the database. Three individuals had deletions in Nef, and one had a 4-amino-acid insertion in Vpu. The unusual polymorphisms in Gag, Env, and Nef described here were also found in stored PBMC samples taken 3 to 11 years prior to, or in one case 4 years subsequent to, the time of sampling for the original sequencing. In all, seven of the eight individuals exhibited one or more unusual polymorphisms; a total of 13 unusual polymorphisms were documented in these seven individuals. These polymorphisms may have been present from the time of initial infection or may have appeared in response to immune surveillance or other selective pressures. Our results indicate that unusual, difficult-to-revert polymorphisms in HIV-1 can be found associated with slow progression or nonprogression in a majority of such cases.
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PMID:Unusual polymorphisms in human immunodeficiency virus type 1 associated with nonprogressive infection. 1075 51

The frequency of CCR5 and CCR2 alleles in human immunodeficiency virus (HIV)-positive and HIV-negative populations of Northern Greece was investigated. The frequency of the CCR5Delta32 allele among the HIV-negative subjects was 0.052, while it was approximately two-fold lower among the seropositives, suggesting that the heterozygous genotype confers a partial resistance to the HIV infection. No significant difference in CCR2 allele frequency between the two groups was observed.
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PMID:HIV-1 co-receptor CCR5 and CCR2 mutations among Greeks. 1076 12

Polymorphisms of the chemokine receptor genes CCR5 and CCR2 are associated with resistance to HIV-1 infection or delayed progression to AIDS. Few data are available on their combined prevalence in healthy subjects; we therefore examined the occurrence of CCR5-Delta32 and CCR2-64I polymorphisms in a sample of 310 healthy Belgians. Allele frequencies were 0.119 and 0.074 for CCR5-Delta32 and CCR2-64I, respectively. Genotype distributions for both polymorphisms were found to be in accordance with Hardy-Weinberg equilibrium, but a significant (p = 0.002) linkage disequilibrium between CCR5-Delta32 and CCR2-64I was observed. The high prevalence of CCR5-Delta32 and CCR2-64I in Belgians may need to be taken into account in the design of studies of antiretroviral treatments.
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PMID:Prevalence of CCR5 and CCR2 HIV-coreceptor gene polymorphisms in Belgium. 1087 74

We have used coreceptor-targeted inhibitors to investigate which coreceptors are used by human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency viruses (SIV), and human immunodeficiency virus type 2 (HIV-2) to enter peripheral blood mononuclear cells (PBMC). The inhibitors are TAK-779, which is specific for CCR5 and CCR2, aminooxypentane-RANTES, which blocks entry via CCR5 and CCR3, and AMD3100, which targets CXCR4. We found that for all the HIV-1 isolates and all but one of the HIV-2 isolates tested, the only relevant coreceptors were CCR5 and CXCR4. However, one HIV-2 isolate replicated in human PBMC even in the presence of TAK-779 and AMD3100, suggesting that it might use an undefined, alternative coreceptor that is expressed in the cells of some individuals. SIV(mac)239 and SIV(mac)251 (from macaques) were also able to use an alternative coreceptor to enter PBMC from some, but not all, human and macaque donors. The replication in human PBMC of SIV(rcm) (from a red-capped mangabey), a virus which uses CCR2 but not CCR5 for entry, was blocked by TAK-779, suggesting that CCR2 is indeed the paramount coreceptor for this virus in primary cells.
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PMID:Use of inhibitors to evaluate coreceptor usage by simian and simian/human immunodeficiency viruses and human immunodeficiency virus type 2 in primary cells. 1088 29

To investigate the genetic susceptibility of different ethnic populations to human immunodeficiency virus-1(HIV-1) infection by comparing the characteristics of gene mutation frequency and polymorphism of CCR5, CCR2 and SDF-1 alleles among different nationalities in the world. The recently reported data on AIDS progression in patients, and on gene mutation and polymorphism of CCR5, CCR2b and SDF-1 genes were collected. The data also included the HIV-1-associated genes polymorphisms of the Chinese individuals detected by the present authors. There was a significant link between the gene mutation, polymorphism of HIV-1-associated genes, genetic susceptibilities and the AIDS progression in patients, although the differences of HIV-1-associated gene mutation, polymorphisms existed among different ethnic populations in the world. The Chinese individuals are more likely to be infected by the M-tropic HIV-1 strain than the American Caucasian. The Chinese individuals have very low gene mutation of CCR5Delta32, which would be helpful for the prevention and gene therapy against the HIV-1 infection.
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PMID:[Polymorphism of human alleles associated with genetic resistance against HIV-1 infection and its implications]. 1093 17

A genetic survey was performed of 200 healthy Thai blood donors for the frequency of three alleles that influence susceptibility to HIV infection and the rate of progression to HIV disease. The CCR5-Delta32 allele was not detected in this population. The CCR2-64I allele was detected at a frequency similar to that found in other Asian populations (15.7%). SDF1-3'A was detected at 33.2%, supporting a cline of increasing frequency of this allele from African and Caucasian to Asian (particularly Australasian) populations. These results have implications for the role of host genetic background in the biology and pathology of HIV in Thailand, and indicate that a systematic survey of non-Caucasian populations may reveal novel alleles important in HIV disease.
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PMID:Prevalence of CCR2-64I, SDF1-3'A and CCR5-Delta32 alleles in healthy Thais. 1094 85

Several mutant genes in HIV co-receptors (e.g., CCR5, CCR2 and CXCR4) have been correlated with susceptibility to HIV or/and rate of progression to AIDS. Some of these genes have high allele frequencies in general populations. Their effects on the HIV/AIDS dynamics may be significant. To study such genetic heterogeneity, Hsu Schmitz [S.-F. Hsu Schmitz, A mathematical model of HIV transmission in homosexuals with genetic heterogeneity, J. Theoret. Med. (to appear)] proposed a one-sex model with susceptibles classified by genotype as having no, partial or full natural resistance to HIV infection and infecteds classified as rapid, normal or slow progressors. The example of CCR5-Delta32 mutation in San Francisco gay men indicated that the normal progressors are most responsible for disease spread. The per-partnership transmission rates of rapid and slow progressors are identified as key parameters. The present manuscript extends the previous one by considering the intervention of treatment or/and vaccination. Detailed investigations are illustrated by using the same example of CCR5-Delta32 mutation in San Francisco gay men. Treating only newly infected individuals or vaccinating only newly recruited susceptibles is not effective enough for disease control. When both measures are applied, the epidemic may be eradicated if the transmission rate of slow progressors is not too large, and treatments and vaccines in use are of decent quality.
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PMID:Effects of treatment or/and vaccination on HIV transmission in homosexuals with genetic heterogeneity. 1094 83

In this review, we describe and discuss the genetic factors that, up to some point, determine resistance to the infection and control the progression of the disease in HIV-infected individuals. Genetic factors may account for non-progression or slow progression of the disease in some of so called long-term non progressors HIV-infected individuals. In general, this group shows no symptoms for more than 10 years, while their circulating T CD4+ cells levels remain stable and they usually have a low virus load. Even though non-progression and rapid progression phenomenon are still not fully understood, there probability exists that some class I and class II MHC alleles are associated with a greater or smaller risk to develop AIDS. Class I HLA-B*35 and Cw*04 alleles are the ones commonly associated with the rapid transition of the infection into AIDS. In contrast, heterozygosity for class I HLA alleles and, particularly, the absence of HLA-B*35 and Cw*04 may contribute to non-progression. Studies which set forward other HLA alleles as possibly taking part of the pathogenic mechanism of non-progression are also described; although, relevant methodological problems can be noticed. Furthermore, this review explains and discusses allelic variations for some of the components of the chemokine receptors family, particularly the genes which codify for CCR5 and CCR2 and other genetic factors such as the SDF1-3'. A variant of the alpha SDF1 chemokine gene that have been associated with AIDS' slow progression or non-progression in HIV-infected individuals. As a whole, the factors described in this review are those that influence the natural history of the disease due to HIV and give an example of what genetic or multigenetic influence can have over the pattern of evolution of HIV infection. Finally, we mention the possible implications that the identification of the genetic markers has in the pathogenesis of HIV disease and in the development of the new therapeutic strategies to control or eliminate HIV.
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PMID:[Genetic determinant factors of resistance to HIV infection and of control of progression to AIDS: implications on pathogenesis and therapeutic approaches for the eradication of HIV. A review]. 1095 12


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