scholarly journals CCR5Δ32 Deletion as a Protective Factor in Czech First-Wave COVID-19 Subjects

2021 ◽  
pp. 111-115
Author(s):  
J HUBACEK ◽  
L DUSEK ◽  
O MAJEK ◽  
V ADAMEK ◽  
T CERVINKOVA ◽  
...  
Keyword(s):  
Individual Differences ◽  
Severe Acute Respiratory Syndrome ◽  
Chemokine Receptor ◽  
Protective Factor ◽  
Population Based ◽  
Genetic Mutation ◽  
Promising Candidate ◽  
Truncated Protein ◽  
Cc Chemokine Receptor 5 ◽  
Hiv 1

Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease (COVID-19), has spread widely around the globe. Significant inter-individual differences have been observed during the course of the infection, which suggests that genetic susceptibility may be a contributing factor. CC chemokine receptor 5 (CCR5), which acts as a co-receptor for the entry of HIV-1 into cells, is promising candidate whose can have an influence on SARS-CoV-2 infection. A genetic mutation known as CCR5Δ32, consisting of a 32-nucleotide deletion, encodes a truncated protein that protects homozygous carriers of the deletion from HIV-1 infection. Similarly, inhibition of CCR5 seems to be protective against COVID-19. In our study, we successfully genotyped 416 first-wave SARS-CoV-2-positive infection survivors (164 asymptomatic and 252 symptomatic) for CCR5Δ32, comparing them with a population based sample of 2,404 subjects. We found the highest number (P=0.03) of CCR5Δ32 carriers in SARS-CoV-2-positive/COVID-19-asympto-matic subjects (23.8 %) and the lowest number in SARS-CoV-2-positive/COVID-19-symptomatic patients (16.7 %), with frequency in the control population in the middle (21.0 %). We conclude that the CCR5Δ32 I/D polymorphism may have the potential to predict the severity of SARS-CoV-2 infection.

scholarly journals Structure and Function of CC-Chemokine Receptor 5 Homologues Derived from Representative Primate Species and Subspecies of the Taxonomic Suborders Prosimii and Anthropoidea

2003 ◽  
Vol 77 (22) ◽  
pp. 12310-12318 ◽  
Author(s):  
Kevin J. Kunstman ◽  
Bridget Puffer ◽  
Bette T. Korber ◽  
Carla Kuiken ◽  
Una R. Smith ◽  
...  
Keyword(s):  
Amino Acid ◽  
Chemokine Receptor ◽  
Transmembrane Domain ◽  
Structure And Function ◽  
Primate Species ◽  
Amino Acid Substitutions ◽  
Immunodeficiency Virus ◽  
And Function ◽  
Cc Chemokine Receptor 5 ◽  
Hiv 1

ABSTRACT A chemokine receptor from the seven-transmembrane-domain G-protein-coupled receptor superfamily is an essential coreceptor for the cellular entry of human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) strains. To investigate nonhuman primate CC-chemokine receptor 5 (CCR5) homologue structure and function, we amplified CCR5 DNA sequences from peripheral blood cells obtained from 24 representative species and subspecies of the primate suborders Prosimii (family Lemuridae) and Anthropoidea (families Cebidae, Callitrichidae, Cercopithecidae, Hylobatidae, and Pongidae) by PCR with primers flanking the coding region of the gene. Full-length CCR5 was inserted into pCDNA3.1, and multiple clones were sequenced to permit discrimination of both alleles. Compared to the human CCR5 sequence, the CCR5 sequences of the Lemuridae, Cebidae, and Cercopithecidae shared 87, 91 to 92, and 96 to 99% amino acid sequence homology, respectively. Amino acid substitutions tended to cluster in the amino and carboxy termini, the first transmembrane domain, and the second extracellular loop, with a pattern of species-specific changes that characterized CCR5 homologues from primates within a given family. At variance with humans, all primate species examined from the suborder Anthropoidea had amino acid substitutions at positions 13 (N to D) and 129 (V to I); the former change is critical for CD4-independent binding of SIV to CCR5. Within the Cebidae, Cercopithecidae, and Pongidae (including humans), CCR5 nucleotide similarities were 95.2 to 97.4, 98.0 to 99.5, and 98.3 to 99.3%, respectively. Despite this low genetic diversity, the phylogeny of the selected primate CCR5 homologue sequences agrees with present primate systematics, apart from some intermingling of species of the Cebidae and Cercopithecidae. Constructed HOS.CD4 cell lines expressing the entire CCR5 homologue protein from each of the Anthropoidea species and subspecies were tested for their ability to support HIV-1 and SIV entry and membrane fusion. Other than that of Cercopithecus pygerythrus, all CCR5 homologues tested were able to support both SIV and HIV-1 entry. Our results suggest that the shared structure and function of primate CCR5 homologue proteins would not impede the movement of primate immunodeficiency viruses between species.

scholarly journals Lipopolysaccharide Inhibits HIV-1 Infection of Monocyte- Derived Macrophages Through Direct and Sustained Down-Regulation of CC Chemokine Receptor 5

2000 ◽  
Vol 164 (5) ◽  
pp. 2592-2601 ◽  
Author(s):  
Giovanni Franchin ◽  
Gabriele Zybarth ◽  
Wei Wei Dai ◽  
Larisa Dubrovsky ◽  
Norbert Reiling ◽  
...  
Keyword(s):  
Chemokine Receptor ◽  
Down Regulation ◽  
Cc Chemokine ◽  
Cc Chemokine Receptor 5 ◽  
Hiv 1 ◽  
Chemokine Receptor 5

scholarly journals Lower than expected maraviroc concentrations in cerebrospinal fluid exceed the wild-type CC chemokine receptor 5-tropic HIV-1 50% inhibitory concentration

AIDS ◽  
2012 ◽  
Vol 26 (7) ◽  
pp. 890-893 ◽  
Author(s):  
David Croteau ◽  
Brookie M. Best ◽  
Scott Letendre ◽  
Steven S. Rossi ◽  
Ronald J. Ellis ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Chemokine Receptor ◽  
Inhibitory Concentration ◽  
Wild Type ◽  
Cc Chemokine ◽  
Cc Chemokine Receptor 5 ◽  
Hiv 1 ◽  
Chemokine Receptor 5

scholarly journals CC Chemokine Receptor 5-Mediated Signaling and HIV-1 Co-receptor Activity Share Common Structural Determinants

1997 ◽  
Vol 272 (32) ◽  
pp. 19771-19776 ◽  
Author(s):  
Ghalib Alkhatib ◽  
Seema S. Ahuja ◽  
Dana Light ◽  
Srinivas Mummidi ◽  
Edward A. Berger ◽  
...  
Keyword(s):  
Chemokine Receptor ◽  
Receptor Activity ◽  
Structural Determinants ◽  
Cc Chemokine ◽  
Cc Chemokine Receptor 5 ◽  
Hiv 1 ◽  
Chemokine Receptor 5

Analysis of the CC chemokine receptor 5 m303 mutation in infants born to HIV-1-seropositive mothers

AIDS ◽  
1999 ◽  
Vol 13 (7) ◽  
pp. 871 ◽  
Author(s):  
L. Ometto ◽  
R. Bertorelle ◽  
M. Mainardi ◽  
M. Giurisato ◽  
L. Chieco-Bianchi ◽  
...  
Keyword(s):  
Chemokine Receptor ◽  
Cc Chemokine ◽  
Cc Chemokine Receptor 5 ◽  
Hiv 1 ◽  
Chemokine Receptor 5

scholarly journals Sialylated O-Glycans and Sulfated Tyrosines in the NH2-Terminal Domain of CC Chemokine Receptor 5 Contribute to High Affinity Binding of Chemokines

2001 ◽  
Vol 194 (11) ◽  
pp. 1661-1674 ◽  
Author(s):  
Norbert Bannert ◽  
Stewart Craig ◽  
Michael Farzan ◽  
Dodzie Sogah ◽  
Niki Villanueva Santo ◽  
...  
Keyword(s):  
Chemokine Receptor ◽  
Posttranslational Modifications ◽  
Chemokine Receptors ◽  
Cc Chemokine ◽  
High Affinity ◽  
Chemokine Receptor Ccr5 ◽  
Leukocyte Chemotaxis ◽  
Chemokine Ligands ◽  
Cc Chemokine Receptor 5 ◽  
Hiv 1

The chemokine receptor CCR5 plays an important role in leukocyte chemotaxis and activation, and also acts as a coreceptor for human and simian immunodeficiency viruses (HIV-1, HIV-2, and SIV). We provide evidence that CCR5 is O-glycosylated on serine 6 in the NH2 terminus. The O-linked glycans, particularly sialic acid moieties, significantly contribute to binding of the chemokine ligands. By contrast, removal of O-linked oligosaccharide exerted little effect on HIV-1 infection. Sulfation of specific tyrosine residues in the CCR5 NH2 terminus was important for efficient β-chemokine binding. Thus, as has been observed for the binding of selectins and their ligands, O-linked carbohydrates and tyrosine sulfates play major roles in promoting the interaction of chemokines with CCR5. The resulting flexible arrays of negative charges on the CCR5 surface may allow specific, high-affinity interactions with diverse chemokine ligands. Although this is the first example of O-linked oligosaccharides and tyrosine sulfates playing a role in chemokine binding, the high density of serines, threonines and tyrosines in the N-termini of many CC chemokine receptors suggests that these posttranslational modifications may commonly contribute to chemokine binding.

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