i CCR5 Genotype and HIV-1 Infection in Perinatally-exposed Infants A. Mas’, T. Espaiiol’, A. Heredial, M. Antonia Pedraza3, M. Hernandez’, I. Caragol’, M. Fernando*, J. M. Bertran’, J. Alcam? and V. Soriano”’ The U’RT chemokinc receptor is required by non-syncytium lllL’-1 strains to infect target cells. ,\ 32 base pair dclrtion (132) in the CCR5 gene causes a structural <‘CR5 modification that does not permit 111\‘-1 rntr?, into cells. The rate of the CC‘R5 ,132 was in\.estigated in 1 37 children born from III\‘-infected mothers. Overall. five (10.6%) of 17 HI\‘-infected infants showed the defect in heterozygosis vs. eight (8.9%) of 90 uninfected children. No (‘CR5 132 homozygotrs were found. InterestingI?,. among infected children, five (21 .X1) of 2 3 showing ;I slow disease progression were heterox~~gous for the CCRS 132, meanwhile none of the 24 infimts with rapid disrasc course had the deletion (P= 0.022). In conclusion, the <‘CR5 A 32 defect does not protect against vertical HI\‘-1 transmission. hut is associated lvith a delayed disease progression in HI\‘-infected children. Introduction Inkctiotl with HI\‘- 1 requires the espression of the CD4 molec~~le ~ILIS a coreccptor on the cellular surface. Km- sq’n~~~tiui~~-iridLIC‘illg (XSI) slrains ol’ the virus use the chemokine receptor c’c’K-5 as coreceptor. whereas syn- cq’tium-inciucin~ (SI) strains can LISA both CC’R-5 and CXC’R-4 (also ternicd fusin ) as coreceptor molecules. ’ Besides. some strains ol’ HIV1 cai use the chemokine receptors C’C’K-213 anti CCR- 3.’ Transmitting strains 01 the \rirus seem to he of the SSI phenotype in most cases.’ I\ )1 base-pair deletion (A 3.2) in the CC’R-5 structural gnta has been associated with resistance to HI\‘- 1 in- kction in indi\kiuals lioinoxygous fur the dcletion.4 ’ Ilmce\~r. this rcsistallce is not absolute. as a kw HIV-1 inkctiolw 11a\,e heen reported in (W-5 A 31 homo- zygotes.‘ ‘(’ It is unclear mkther (‘U-5 A52 het- croxggosily coii~ers some degree of protection against inkction. Samson r’t tr/.’ showed that the frequencg of C’CK-5 A 32 heterozygotes among HIV- 1-ini’wted Cau- casian subjects was 3 5% lower than in the general C’aucasian population. suggesting ii partial protection in heterozygotes. I~O~TITI-. that protection WIS not l’ound in the adult cohorts ol’ hoinosexuals, intrawnous di-ug users. and Iiaemophiliacs reported by Dean et rd..’ or in the cohort oi homosexuals reported by H~~ang c’t rd.” Methods We have in\aestigated the resistance to HI\‘-1 infection conferred bv the C’C’R-5 A 32 allele in ii cohort of peri- natally-exposed inl’ants. r\lthough n~aternal. immuno- logical and \kal factors seem to inllucnce the perinatal transmission of’ L {IV 1 that occurs in approximatel!~ ‘Ok 2 5% of cases in wonicn without antiviral treatment. their specilic contribution is still not clear. ” Some studies ha\~ reported a direct correlation between the maternal spiral loxi and the risk of transmission.” ” but occurrcncc’ 01 transmission and non-transmission over the entire range of maternal HI\‘- 1 Rh\;X wlues has been demonstrated in studies including a greater number 01’ inkcted WOII~~I~.‘~ The protectiw role ol’ the C’CK-5 A52 allele M’:IS in- vestigated in the offspring ol‘ 1 37 scropositivc mothers that had new received antiviral treatment and had not breast-fed their children. ~111 had attended in a single III\‘/ AlUS l’aediatric Reltrence Centre located in kwcclone between 19X 1 and 1996. The diagnosis ol’HI\‘- 1 inkction in the infants followed the WC criteria.” The CC’II-5 genotype \vas examined in cell DNA ti-oni each child. Briefly. PCR wnplilicution of the (‘CR-5 gale. including the deletion fragment. was carried out using specilic oligonucleotide primers CCK-51) ( S’-C’C”I‘(X; C”I‘(X‘C’ CX’C’C’I-\TCX’I’G- 3’) and C’C’K-51. ( 5’-CC’;\C;C’ ;ICX’GC~ C‘A(X;A C’C’rICX-3’). Conditions Ibr I’CR amplification were 10 nix1 ‘I‘ris-IiC’I (pli 8. 3 1. 50 inn1 I<C’I. 1.5 111x1 MgU,. 0.1 n.v of’ each of the Ibur deox~nucleotide triphosphates. 60 ng of each prilner and 0. i5 ol‘ Try polymerase (I’erkin- Elmer llispania. Madrid. Spain), in a linal reaction volume