aDepartment of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy
bDepartment of Oncology and Surgical Sciences, AIDS Reference Center, University of Padua, Padua, Italy.
Received 28 November, 2008
Revised 12 December, 2008
Accepted 12 December, 2008
Correspondence to Silvia Baroncelli, Pharmacology and Therapy of Viral Diseases Unit, Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. Tel: +39 06 4990 3304; fax: +39 06 4938 7199; e-mail: email@example.com
In a recent letter, Segat et al.  reported new data on the frequencies of single nucleotide polymorphisms (SNPs) of the human β defensin-1 (DEFB1) gene in a population of Brazilian HIV-1-infected children and compared these data with the results of other studies, including those previously performed on HIV-1-infected children by the same research group.
This new study did not confirm the significant association between the −52GG and −20AA genotypes of the DEFB1 gene and HIV-1 infection, found in a previous study performed on Brazilian HIV-1-infected and uninfected children . Furthermore, these new data also differed from those previously reported on Italian HIV-1-infected and healthy children, in whom the −44C/G SNP was found to influence HIV-1 infection . In light of these findings, the authors conclude that the role of DEFB1 gene polymorphisms should be redefined. Considering the variability found in different and even the same populations, we agree that more caution should be taken regarding this issue. However, although genetic differences between different populations could partially explain the different results, it should be taken into account that inconsistent results may be generated by the small size of the studied population and by the lack of relevant controls.
It appears more difficult to extend the concerns of Segat et al.  about the role of DEFB1 in HIV-1 infection to our study , which analyzed the frequencies of DEFB1 gene polymorphisms in HIV-1-infected Mozambican women and the association of these frequencies with viral load. In antiretroviral-untreated women (n = 38), we found a significant association between the −52GG genotype and a lower viral load in breast milk. Segat et al.  state that our results are not convincing as even women with the −52AA genotype had lower viral load in breast milk than those with the −52GA genotype. This is true, but the difference was statistically significant only for the −52GG genotype.
Different from the authors' assertions, our data are consistent with the finding that the −52AA and −52GA genotypes are correlated with reduced expression of DEFB1 [5,6]. Contrary to what Segat et al.  stated regarding the possible different expression of DEFB1 in different districts (blood and mammary gland tissue), our results are supported by other authors who found higher concentrations of DEFB1 in breast milk than in other mucosal surfaces, [7,8], with a marked increase in DEFB1 expression during lactation . Moreover, the relative incapacity of DEFB1 to inhibit in-vitro HIV-1 infection (, but not fully confirmed by other authors ), is not in contrast with our results. Indeed, in our study, we reported a lower HIV-1 viral load in the breast milk of women with the −52GG genotype, but we did not describe a direct effect of DEFB1 on HIV-1 replication. It is well known that inflammation, such as mastitis or local infection, can favor HIV-1 replication in mammary tissues [11,12]; thus, the antimicrobial function of β-defensins could exert an indirect effect on HIV-1 replication.
1. Segat L, Brandao LAC, Guimaraes RL, Crovella S. Are DEFB1 gene polymorphisms associated with HIV infection and viral replication? AIDS
2. Milanese M, Segat L, Pontillo A, Arraes LC, de Lima Filho JL, Crovella S. DEFB1 gene polymorphisms and increased risk of HIV-1 infection in Brazilian children. AIDS 2006; 20:1673–1675.
3. Braida L, Boniotto M, Pontillo A, Tovo PA, Amoroso A, Crovella S. A single-nucleotide polymorphism in the human beta-defensin 1 gene is associated with HIV-1 infection in Italian children. AIDS 2004; 18:1598–1600.
4. Baroncelli S, Ricci E, Andreotti M, Guidotti G, Germano P, Marazzi MC, et al
. Single-nucleotide polymorphisms in human beta-defensin-1 gene in Mozambican HIV-1-infected women and correlation with virologic parameters. AIDS 2008; 22:1515–1517.
5. Milanese M, Segat L, Crovella S. Transcriptional effect of DEFB1 gene 5′ untranslated region polymorphisms. Cancer Res 2007; 67:5997.
6. Kocsis AK, Kiss ZF, Tiszlavicz L, Tiszlavicz Z, Mandi Y. Potential role of human beta-defensin 1 in Helicobacter pylori-induced gastritis. Scand J Gastroenterol 2008; 8:1–7.
7. Tunzi CR, Harper PA, Bar-Oz B, Valore EV, Semple JL, Watson-MacDonell J, et al
. Beta-defensin expression in human mammary gland epithelia. Pediatr Res 2000; 48:30–35.
8. Jia HP, Starner T, Ackermann M, Kirby P, Tack BF, McCray PB Jr. Abundant human beta-defensin-1 expression in milk and mammary gland epithelium. J Pediatr 2001; 138:109–112.
9. Quiñones-Mateu ME, Lederman MM, Feng Z, Chakraborty B, Weber J, Rangel HR, et al
. Human epithelial beta-defensins 2 and 3 inhibit HIV-1 replication. AIDS 2003; 17:F39–F48.
10. Sun L, Finnegan CM, Kisk-Catalone T, Blumenthal R, Garzino-Demo P, La Terra Maggiore GM, et al
. Human beta-defensins supress human immunodeficiency virus infection: potential role in mucosal protection. J Virol 2005; 22:14318–14329.
11. Phiri W, Kasonka L, Collin S, Makasa M, Sinkala M, Chintu C, et al
. Factors influencing breast milk HIV RNA viral load among Zambian women. AIDS Res Hum Retroviruses 2006; 22:607–614.
12. Kantarci S, Koulinska IN, Aboud S, Fawzi WW, Villamor E. Subclinical mastitis, cell-associated HIV-1 shedding in breast milk, and breast-feeding transmission of HIV-1. J Acquir Immune Defic Syndr 2007; 46:651–654.