theta-Defensin pseudogenes in HIV-1-exposed, persistently seronegative female sex-workers from Thailand.

Abstract

The leukocytes of rhesus monkeys contain cyclic octadecapeptides (theta;-defensins) that can protect cells from infection by HIV-1 in vitro. Although humans express mRNA from one or more theta;-defensin pseudogenes, these transcripts contain a premature stop codon that prevents formation of theta;-defensin peptides. We hypothesized that some highly exposed persistently seronegative (HEPS) individuals might have intact theta;-defensin (DEFT) genes and produce functional theta;-defensins that might account for their resistance to HIV-1 infection. We sequenced DEFT genes from 30 women in Chiang Rai, northern Thailand: 11 HEPS female sex-workers and 19 control women (10 HIV-1 infected and 9 HIV-1 uninfected). We found that theta;-defensin genes from all 11 HEPS women contained the crucial signal sequence stop codon, as did the 19 control women. Synthetic theta;-defensins based on the cDNA sequences to generate a human theta;-defensin (termed retrocyclin-1 and -2) were capable of inhibiting replication of Thai HIV-1 subtype B and CRF01_AE isolates regardless of the coreceptor utilization of the isolates. Although our study indicates that synthetic theta;-defensin peptides are effective in vitro against Thai subtype B and CRF01_AE isolates of HIV-1, the presence of premature stop codons in the DEFT genes of these HEPS women makes it unlikely that endogenous theta;-defensin production accounts for their resistance to HIV-1.

• Authors: Chunfu Yang, Louvonia Boone, Tung X Nguyen, Donna Rudolph, Khanchit Limpakarnjanarat, Timothy D Mastro, Jordan Tappero, Alexander M Cole, Renu B Lal
• Journal: Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases (Infect Genet Evol) Vol. 5 Issue 1 Pg. 11-5 (Jan 2005) ISSN: 1567-1348 [Print] Netherlands
• PMID: 15567134 (Publication Type: Journal Article)

Chemical References

• Codon, Terminator
• Defensins
• theta-defensin

Topics

• Amino Acid Sequence
• Cell Line
• Codon, Terminator
• Defensins (genetics, pharmacology)
• Female
• HIV Seronegativity (genetics, immunology)
• HIV-1 (drug effects, physiology)
• Humans
• Molecular Sequence Data
• Pseudogenes (genetics)
• Sex Work
• Thailand
• Virus Replication (drug effects)