HBDs
Polymorphisms in the DEFB1 gene (coding for HBD1) have been associated with susceptibility to and severity of pulmonary diseases [140-144]. Interestingly, single-nucleotide polymorphisms (SNPs) in the 5’ untranslated region of DEFB1 influence transmission rates to children and this is most likely due to the influence of these genetic variants on expression of HBD1 and ultimately on plasma and/or breast milk levels viral loads [145-148].
Although HBD1 has no effect on HIV infection in vitro [73, 118], the presence of SNPs may modulate the overall immune response by down-or up regulation of HBD1.The role of defensins in protection against HIV infection has been studied in HIV-exposed seronegative (ESN) individuals. ESN expressed significantly greater mRNA copy number of HBD2 and 3 in oral mucosa compared to healthy controls, while there was no difference in mRNA copy number of HBDs 1-3 in vaginal/endocervical mucosa between ESN and controls [149]. In addition, homozygosity for the A692G polymorphism is significantly more frequent in ESN than in seropositive individuals [149]. Sequence analysis of θ-defensin pseudogenes (DEFT) in ESN female sex-workers from Thailand revealed that all subjects had premature stop codons [150]. Therefore, restoration of endogenous θ-defensin production does not account for the resistance to HIV-1 infection in these women.