CCR2 , CCR5 , and CXCL12 variation and HIV/AIDS in Papua New Guinea

2019

Cells

C-C chemokine receptor 5 (CCR5) polymorphisms, particularly a 32-base pair deletion (∆32) in the open reading frame and −2459G > A in the promoter, are well known for their associations with HIV-1 infection and/or disease progression in a variety of studies. In this era of an HIV cure, where all the emphasis is on ∆32, it seems that −2459G > A has been forgotten or ignored. There is significant importance in the incorporation of the CCR5 −2459G > A genotype information into studies evaluating new immunologic and chemotherapeutic strategies, and those designing and implementing better treatment strategies with current antiretroviral therapy, doing so would enable a better understanding of the response to the intervention, due to a mechanistic or constitutive explanation. Until we find a strategy, whether a stem-cell transplantation or CCR5 editing approach or something else, that delivers a cure to the millions, we should make use of every piece of information that may help curtail HIV/AIDS as a threat to public health.

mentioning

confidence: 99%

mentioning

confidence: 99%

CCR5 Promoter Polymorphism −2459G > A: Forgotten or Ignored?

2019

Cells

“…On the other hand, allele frequency of CCR5 −2459A ranges from 32% to 66% in most populations (see Table 1 ). In Papua New Guinea, an Oceania country, this allele frequency was much higher, 85% in one study ( Clark and Dean, 2004 ) and 98% in another ( Mehlotra et al, 2015 ).…”

Section: Genetic Variation Ccr5 and Hiv/aids Outcomesmentioning

confidence: 73%

Chemokine receptor gene polymorphisms and COVID-19: Could knowledge gained from HIV/AIDS be important?

Infection, Genetics and Evolution

2020

Self Cite

Emerging results indicate that an uncontrolled host immune response, leading to a life-threatening condition called cytokine release syndrome (also termed “cytokine storm”), is the major driver of pathology in severe COVID-19. In this pandemic, considerable effort is being focused on identifying host genomic factors that increase susceptibility or resistance to the complications of COVID-19 and translating these findings to improved patient care. In this regard, the chemokine receptor-ligand nexus has been reported as potentially important in severe COVID-19 disease pathogenesis and its treatment. Valuable genomic insights into the chemokine receptor-ligand nexus have been gained from HIV infection and disease progression studies. Applying that knowledge, together with newly discovered potential host genomic factors associated with COVID-19, may lead to a more comprehensive understanding of the pathogenesis and treatment outcomes in COVID-19 patients.

“…18,20 Among all nine CCR5 haplotypes (HHA-HHG*2), the consistency of the association of -2459A allelecarrying HHE homozygosity (E/E genotype) with an unfavorable outcome across diverse populations is noteworthy, which suggests that the HHE haplotype confers similar phenotypic effects against distinct genetic backgrounds. [20][21][22][23][24] Given this already known functional significance of -2459G/A (hereafter referred to as rs1799987G/A), a likely reason for not including this promoter polymorphism in the key analyses by Kulkarni et al 9 could be that the rs1015164 SNP was found to have a genome-wide effect independent of Hap-P1 (carrying rs1799987A) by McLaren et al 8 The analyses by Kulkarni et al have found that (a) rs1015164A/G variation associates with HIV-1 viral load and CD4 + T cell counts across distinct populations ( fig. 1 and Supplementary fig.…”

Section: Mehlotramentioning

confidence: 99%

New Knowledge About CCR5, HIV Infection, and Disease Progression: Is “Old” Still Valuable?

AIDS Research and Human Retroviruses

2020

Self Cite

CC chemokine receptor (CCR) 5 (CCR5) is the main HIV-1 coreceptor involved in virus entry and cell-to-cell spread during acute and chronic infections: such CCR5 and T cell tropic viruses are adapted to and replicate in CD4 + memory T cells. Polymorphisms in CCR5 regulate CCR5 expression, which, in turn, influences HIV infection acquisition and subsequent disease progression. Among these polymorphisms, a 32-bp deletion in the CCR5 open reading frame (CCR5 D32) and a single nucleotide polymorphism (SNP) in the promoter (-2459G/A) are the most well-characterized polymorphisms. CCR5 D32 provides partial to full protection against HIV infection and, therefore, serves as a basis for gene deletion studies attempting to achieve a permanent HIV cure. Recent studies have discovered that certain SNPs in the CCR region, not within CCR5, also affect CCR5 expression, HIV infection, and disease progression. Although these studies provide further valuable information regarding the role of human genetic variation in HIV/AIDS, they did not incorporate-2459G/A. In this article, the author summarizes the knowledge gained through the discovery of these new SNPs and introduces the idea that by not incorporating-2459G/A, less comprehensive conclusions may have been reached. Until a strategy that delivers a cure to the millions is found, every piece of information that may help curtail the HIV/AIDS threat to public health should be considered useful.