Maleic anhydride-modified chicken ovalbumin as an effective and inexpensive anti-HIV microbicide candidate for prevention of HIV sexual transmission.
BACKGROUND
Previous studies have shown that 3-hydroxyphthalic anhydride (HP)-modified bovine milk protein, beta-lactoglobulin (beta-LG), is a promising microbicide candidate. However, concerns regarding the potential risk of prion contamination in bovine products and carcinogenic potential of phthalate derivatives were raised. Here we sought to replace bovine protein with an animal protein of non-bovine origin and substitute HP with another anhydride for the development of anti-HIV microbicide for preventing HIV sexual transmission.


RESULTS
Maleic anhydride (ML), succinic anhydride (SU) and HP at different conditions and variable pH values were used for modification of proteins. All the anhydrate-modified globulin-like proteins showed potent anti-HIV activity, which is correlated with the percentage of modified lysine and arginine residues in the modified protein. We selected maleic anhydride-modified ovalbumin (ML-OVA) for further study because OVA is easier to obtain than beta-LG, and ML is safer than HP. Furthermore, ML-OVA exhibited broad antiviral activities against HIV-1, HIV-2, SHIV and SIV. This modified protein has no or low in vitro cytotoxicity to human T cells and vaginal epithelial cells. It is resistant to trypsin hydrolysis, possibly because the lysine and arginine residues in OVA are modified by ML. Mechanism studies suggest that ML-OVA inhibits HIV-1 entry by targeting gp120 on HIV-1 virions and also the CD4 receptor on the host cells.


CONCLUSIONS
ML-OVA is a potent HIV fusion/entry inhibitor with the potential to be developed as an effective, safe and inexpensive anti-HIV microbicide.
Li
Lin
L
School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, China.
Qiao
Pengyuan
P
Yang
Jie
J
Lu
Lu
L
Tan
Suiyi
S
Lu
Hong
H
Zhang
Xiujuan
X
Chen
Xi
X
Wu
Shuguang
S
Jiang
Shibo
S
Liu
Shuwen
S
D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D002645:Chickens; D018562:Disease Transmission, Infectious / Q000517:prevention & control; D004847:Epithelial Cells / Q000187:drug effects; D015658:HIV Infections / Q000517:prevention & control / Q000635:transmission; D015497:HIV-1 / Q000187:drug effects*; D015498:HIV-2 / Q000187:drug effects*; D006801:Humans; D007782:Lactoglobulins / Q000378:metabolism / Q000494:pharmacology; D008299:Maleic Anhydrides / Q000378:metabolism*; D010047:Ovalbumin / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D015302:Simian Immunodeficiency Virus / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects
D019380:Anti-HIV Agents; D000890:Anti-Infective Agents; D007782:Lactoglobulins; D008299:Maleic Anhydrides; D010047:Ovalbumin