A conserved molecular action of native and recombinant Epap-1 in inhibition of HIV-1 gp120 mediated viral entry.
The early expression of Epap-1 (early pregnancy associated protein), a 90 kDa anti-HIV-1 active glycoprotein, in the first trimester placental tissue suggests that it is one of the innate immune factors/proteins protecting the fetus from HIV infections. In the present investigation, we have cloned and expressed Epap-1 in bacterial and baculovirus expression systems. The recombinant Epap-1 as well as native Epap-1 shows a conserved molecular mode of action. These proteins exhibit significant antiviral activity and inhibit the cell fusion reaction between gp120 expressing HeLa (HL2/3) cells and T cell line (SupT1). Further, the rhodamine labeled Epap-1 specifically bound to gp120 expressed on the surface of HL2/3 cells during fusion reaction thereby inhibiting viral entry. Analysis of the interacting gp120 epitopes revealed that Epap-1 binds specifically to epitopes of gp120, recognizing constant-5 (C5) region and the variable-3 (V3) epitope of gp120 expressed on HL2/3 cells; It exhibits specific interaction with C5 region of cell-free virus in four HIV-1 isolates suggesting that the molecular interaction of Epap-1 is specific and is highly conserved in binding to gp120 leading to inhibition of viral entry. Epap-1 can thus be a very efficient natural protection mechanism against cell-free and cell-associated viral infections during early pregnancy.
Roda Rani
K P
KP
Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad 500046, India.
Pelluru
Dheeraj
D
Kondapi
Anand K
AK
D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D023581:HIV Fusion Inhibitors / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins
D006023:Glycoproteins; D015699:HIV Envelope Protein gp120; D023581:HIV Fusion Inhibitors; D011257:Pregnancy Proteins; D011994:Recombinant Proteins; C455642:early pregnancy-associated protein 90 kDa, human