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Clinical and Diagnostic Laboratory Immunology, July 1998, p. 463-466, Vol. 5, No. 4
1071-412X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Human Immunodeficiency Virus Type 1 Disease Progression, CCR5 Genotype, and Specific Immune Responses

Ubaldo Visco-Comandini,1,2 Catharina Hultgren,1,3 Christina Broström,1,4 Markus Birk,1,4 Soo Kim,1 and Matti Sällberg1,3,*

Divisions of Clinical Virology (F 68),1 Clinical and Oral Bacteriology (F 88),3 and Infectious Diseases,4 Karolinska Institutet, Huddinge University Hospital, S-141 86 Huddinge, Sweden, and Department of Infectious and Tropical Diseases, University of Rome "La Sapienza," Rome, Italy2

Received 24 November 1997/Returned for modification 15 January 1998/Accepted 19 March 1998

The correlation among the presence of a 32-bp deletion in the CC-chemokine receptor 5 (CCR5) gene, disease progression, and human immunodeficiency virus type 1 (HIV-1)-specific immune responses was analyzed for a cohort of 79 Caucasian HIV-1-infected patients. The CCR5 genotype (CCR5/CCR5 = wild type/wild type or Delta 32CCR5/CCR5 = 32-bp deletion/wild type) in peripheral blood mononuclear cells was determined by PCR, followed by sequencing of both wild-type and Delta 32CCR5 gene fragments. HIV-1-specific humoral responses to gp41 and V3MN peptides were determined by enzyme immunoassays. The prevalence of the Delta 32CCR5 allele was lower among 37 patients with rapid progression (progression to AIDS or to a CD4 cell count of <200 × 106/liter in less than 9 years; P < 0.01) compared to that for 42 patients with slow progression (no AIDS and CD4 cell count of >200 × 106/liter after at least 9 years from infection) or to that for 25 non-HIV-1-infected Swedish blood donors (P < 0.05). No differences were observed in the wild-type CCR5 sequences between the different groups of patients. For three analyzed patients, the 32-bp Delta 32CCR5 gene deletions were identical. The antibody titers against gp41 and a V3MN peptide in patients with the Delta 32CCR5/CCR5 genotype were not significantly different from those in pair-matched CCR5/CCR5 controls. However, in 13 analyzed patients, a stronger serum neutralizing activity was associated with the Delta 32CCR5/CCR5 genotype. Thus, a CCR5/CCR5 genotype correlates with a shortened AIDS-free HIV-1 infection period and possibly with a worse neutralizing activity, without an evident influence on the antibody response to two major antigenic regions of HIV-1 envelope.


* Corresponding author. Mailing address: Division of Clinical Virology, F 68, Huddinge University Hospital, S-141 86 Huddinge, Sweden. Phone: 46-8-5858 79 39. Fax: 46-8-5858 79 33. E-mail: misg{at}labd01.hs.sll.se.


Clinical and Diagnostic Laboratory Immunology, July 1998, p. 463-466, Vol. 5, No. 4
1071-412X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.



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