Combinatorial content of CCL3L and CCL4L gene copy numbers influence HIV-AIDS susceptibility in Ukrainian children

Shostakovich-Koretskaya, Ludmila; Catano, Gabriel; Chykarenko, Zoya A.; He, Weijing; Gornalusse, Germán G.; Mummidi, Srinivas; Sanchez, Racquel; Dolan, Matthew J.; Ahuja, Seema S.; Clark, Robert A.; Kulkarni, Hemant; Ahuja, Sunil K.

doi:10.1097/qad.0b013e3283270b3f

Cited by 41 publications

(45 citation statements)

References 40 publications

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“…Nine of 17 slow-progressor children (53%) did not possess protective HLA-B alleles, nor did their mothers, and of the progressor children, 8 of 44 (18%) carried a protective HLA-B allele, or the mother did. Non-HLA-associated factors likely to play a role would include non-HLA genetic factors (1,31), the presence of coinfections by pathogens such as hepatitis C virus, cytomegalovirus, and Mycobacterium tuberculosis, and the concomitants of extreme poverty (24).…”

Section: Discussionmentioning

confidence: 99%

Impact of HLA in Mother and Child on Disease Progression of Pediatric Human Immunodeficiency Virus Type 1 Infection

Thobakgale

Prendergast

Crawford

et al. 2009

J Virol

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A broad Gag-specific CD8؉ T-cell response is associated with effective control of adult human immunodeficiency virus (HIV) infection. The association of certain HLA class I molecules, such as HLA-B*57, -B*5801, and -B*8101, with immune control is linked to mutations within Gag epitopes presented by these alleles that allow HIV to evade the immune response but that also reduce viral replicative capacity. Transmission of such viruses containing mutations within Gag epitopes results in lower viral loads in adult recipients. In this study of pediatric infection, we tested the hypothesis that children may tend to progress relatively slowly if either they themselves possess one of the protective HLA-B alleles or the mother possesses one of these alleles, thereby transmitting a low-fitness virus to the child. We analyzed HLA type, CD8؉ T-cell responses, and viral sequence changes for 61 mother-child pairs from Durban, South Africa, who were monitored from birth. Slow progression was significantly associated with the mother or child possessing one of the protective HLA-B alleles, and more significantly so when the protective allele was not shared by mother and child (P ‫؍‬ 0.007). Slow progressors tended to make CD8 ؉ T-cell responses to Gag epitopes presented by the protective HLA-B alleles, in contrast to progressors expressing the same alleles (P ‫؍‬ 0.07; Fisher's exact test). Mothers expressing the protective alleles were significantly more likely to transmit escape variants within the Gag epitopes presented by those alleles than mothers not expressing those alleles (75% versus 21%; P ‫؍‬ 0.001). Reversion of transmitted escape mutations was observed in all slow-progressing children whose mothers possessed protective HLA-B alleles. These data show that HLA class I alleles influence disease progression in pediatric as well as adult infection, both as a result of the CD8 ؉ T-cell responses generated in the child and through the transmission of low-fitness viruses by the mother.

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Section: Discussionmentioning

confidence: 99%

Impact of HLA in Mother and Child on Disease Progression of Pediatric Human Immunodeficiency Virus Type 1 Infection

Thobakgale

Prendergast

Crawford

et al. 2009

J Virol

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“…Less than 5% of the human population lacks the gene for CCL3L or CCL4L. Furthermore, low copy numbers of CCL3L and CCL4L are associated with an increased risk of acquiring human immunodeficiency virus (HIV) and progressing rapidly to AIDS [18]. This illustrates the importance of CCL3L1, described as a most potent CCR5 agonist and inhibitor of HIV-1 infection [19].…”

Section: Introductionmentioning

confidence: 97%

Overview of the mechanisms regulating chemokine activity and availability

2012

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“…In addition, humans and mouse strains have copy number variations in some chemokine genes [10, 11]. The copy numbers of tandemly duplicated CCL3- and CCL4-like genes vary among human individuals and have been implicated in the susceptibility and disease progression of HIV infection [10, 12–14]. …”

Section: Introductionmentioning

confidence: 99%

Genome Diversification Mechanism of Rodent and Lagomorpha Chemokine Genes

Shibata

Nomiyama

Yoshie

et al. 2013

BioMed Research International

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Chemokines are a large family of small cytokines that are involved in host defence and body homeostasis through recruitment of cells expressing their receptors. Their genes are known to undergo rapid evolution. Therefore, the number and content of chemokine genes can be quite diverse among the different species, making the orthologous relationships often ambiguous even between closely related species. Given that rodents and rabbit are useful experimental models in medicine and drug development, we have deduced the chemokine genes from the genome sequences of several rodent species and rabbit and compared them with those of human and mouse to determine the orthologous relationships. The interspecies differences should be taken into consideration when experimental results from animal models are extrapolated into humans. The chemokine gene lists and their orthologous relationships presented here will be useful for studies using these animal models. Our analysis also enables us to reconstruct possible gene duplication processes that generated the different sets of chemokine genes in these species.

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Combinatorial content of CCL3L and CCL4L gene copy numbers influence HIV-AIDS susceptibility in Ukrainian children

Cited by 41 publications

References 40 publications

Impact of HLA in Mother and Child on Disease Progression of Pediatric Human Immunodeficiency Virus Type 1 Infection

Impact of HLA in Mother and Child on Disease Progression of Pediatric Human Immunodeficiency Virus Type 1 Infection

Overview of the mechanisms regulating chemokine activity and availability

Genome Diversification Mechanism of Rodent and Lagomorpha Chemokine Genes

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