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. 2007 Aug;81(16):8827-32.
doi: 10.1128/JVI.00895-07. Epub 2007 May 30.

Mamu-B*08-positive macaques control simian immunodeficiency virus replication

John T Loffredo  1 , Jess Maxwell, Ying Qi, Chrystal E Glidden, Gretta J Borchardt, Taeko Soma, Alex T Bean, Dominic R Beal, Nancy A Wilson, William M Rehrauer, Jeffrey D Lifson, Mary Carrington, David I Watkins
Affiliations

Mamu-B*08-positive macaques control simian immunodeficiency virus replication

John T Loffredo et al. J Virol. 2007 Aug.

Abstract

Certain major histocompatibility complex (MHC) class I alleles are associated with the control of human immunodeficiency virus and simian immunodeficiency virus (SIV) replication. We have designed sequence-specific primers for detection of the rhesus macaque MHC class I allele Mamu-B*08 by PCR and screened a cohort of SIV-infected macaques for this allele. Analysis of 196 SIV(mac)239-infected Indian rhesus macaques revealed that Mamu-B*08 was significantly overrepresented in elite controllers; 38% of elite controllers were Mamu-B*08 positive compared to 3% of progressors (P = 0.00001). Mamu-B*08 was also associated with a 7.34-fold decrease in chronic phase viremia (P = 0.002). Mamu-B*08-positive macaques may, therefore, provide a good model to understand the correlates of MHC class I allele-associated immune protection and viral containment in human elite controllers.

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Figures

FIG. 1.
FIG. 1.
Design of PCR-sequence specific primers (PCR-SSP) to amplify the MHC class I allele Mamu-B*08 from genomic DNA. (A) Primers were designed to amplify a 1,096-bp product that contains part of exon 3 (77 bp), intron 3 (573 bp), exon 4 (276 bp), intron 4 (106), and 64 bp of the transmembrane region (exon 5) of Mamu-B*08. Black triangles represent Mamu-B*08 introns. (B) Sequence similarity between Mamu-B*08 and Mamu-B*03. To avoid amplification of Mamu-B*03, the Mamu-B*08 primers were designed such that the forward primer amplifies Mamu-B*08 or Mamu-B*03 and the reverse primer takes advantage of three unique polymorphisms in the transmembrane region (exon 5), allowing for specific detection of Mamu-B*08 only. (C) PCR-SSP genotyping of Mamu-B*08 from genomic DNA of selected elite controller macaques. Macaques 84557 and r88090 were used as Mamu-B*08 positive and negative controls, respectively. Previously, a cDNA library isolated from 84557 indicated that this macaque expresses Mamu-B*08. Mamu-B*08 was not found in a cDNA library from macaque r88090 (6). PCR-SSP primers that amplify a portion of Mamu-DRB (∼300 bp) were included as an internal control to minimize false negatives. A 100-bp DNA ladder was used to interpret amplicon sizes.
FIG. 2.
FIG. 2.
Mamu-B*08 influences chronic-phase plasma virus concentrations in SIVmac239-infected Indian rhesus macaques. (A) Acute-phase peak viremia (highest plasma virus concentration between weeks 1 and 3 postinfection) is not affected by the presence of the typed MHC class I alleles in 196 SIVmac239-infected Indian rhesus macaques. (B) Contribution of typed MHC class I alleles to variation in chronic-phase plasma viremia in the same cohort of 196 macaques. The chronic-phase geometric mean was calculated, and the plasma virus concentration time points ranged from ≥10 weeks to <7.16 years postchallenge. MHC class I effects on SIV plasma viremia are shown with the changes in geometric mean displayed as dots for each MHC class I allele (Mamu-A*01, -A*02, -A*08, -A*11, -B*01, -B*03/-B*04, -B*08, -B*17, and -B*29) relative to the whole cohort and 95% confidence intervals (bars). Probabilities (P values) for MHC class I alleles with statistically significant reductions from the relative log geometric mean are displayed. Mamu-B*03 and -B*04 were analyzed together because the three Mamu-B*03-positive macaques were also positive for Mamu-B*04.
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