Avian Influenza virus A H5N1 polymerases PA, PB1 and hemagglutinin contain a platelet integrin ITGB3 inducing auto-immune anti-platelet antibodies and thrombocytopenia.

Présentation Poster au 8TH EUROPEAN MEETING ON VIRAL ZOONOSES( Saint Raphaël, France, Octobre 2017)

Guy Mong Ky Tran(1) & Adrien Caprani(2)

(1) Retired since 2014 from University of Auvergne Rhone-Alpes, Health Regional Agency, Public Health Department, Hospital Hotel-Dieu, Clermont-Ferrand ; 31 Av du Bois – Chatenay Malabry, France. email: mkg_tran@yahoo.fr

(2) Association « Positifs », 147 chemin de la futaie, 83550 Vidauban, email: positifpresident@yahoo.fr


Among the prognostic factors in complicated lethal Influenza A H5N1 Vietnam, a low platelet count in patients is highly correlated to mortality ; oseltamivir is completely inefficient and not recommanded in these cases. This thrombocytopenia was investigated by analysing amino acid sequences of platelet glycoprotein gpIIb/IIIa (integrin ITGA2b/ITGB3) at the epitope ITGB3 49-CAPESIEFPVSEARVLED-66 of Nardi MA (PNAS, 1997), which induced a  thrombocytopenia in mice by inducing high affinity auto-antibodies. Many pathogens mimic this Phenylalanine-Proline FP dipeptide (Tran GMK, ISHEID Conf 2010), most of them being hemorragic fevers (for instance, Ebola, hemorragic dengue fever type 2, leptospirosis Adaman hemorragic fever, etc ). Avian Influenza H5N1 was compared to a chicken Ebola ; Ebola (Sudan) L polymerase was 747-SVFPL(S,E)S-754. We found this crucial auto-immune epitope in Influenza A H5N1 Duck/Guandong/07/2000 RNA-dependent polymerase subunit PA 522-SMEFPLTDPRLE-533. Other Influenza  were H5N1 Goose/Guandong/1/96(Gs/Gd),A/India /Pun/2015(H1N1),A /canine/NY /dog /2008(H3N8). The longest alignment was between a chimera (Goose /Guandong with other Influenza) and ITGB3 :

ITGB3                                                           CDLKENLLKDNCAPESIEFPVSEARVLE

Influenza                                                     CQLKWALGENMAPESMEFPLTDPR-LE

There is an alignment between gallus ITGB3 and Influenza H5N1 Hemagglutinin :

Gallus ITGB3                      DF(E,I)FPRSS

Influenza H5N1 HA                   128-EKIQIFPRSS-137

Vietnam Homo/2005              EKIQIIPKSS

Polymerase PB1 (Kawaoka Y, 1989) of A/Mallard/Shangai/2013 (H5N8) has SMELP(F,S). Conclusion : Influenza virus A H5N1 contains a platelet integrin ITGB 3 with a central motif FP which induces high affinity auto-antibodies against platelets and destroying them, at 3 places (polymerases PA, PB1 and HA). As anti-proteases (Saquinavir, Ritonavir, etc) used in HIV-1 infection mimick this  FP (because FP is present in HIV-1 GAG, cleaved by the protease), they may constitute haptens blocking  deleterious anti-platelet auto-antibodies. We suggest that antiproteases were used in hemorragic influenza,  hemorragic Dengue fever 2, Ebola, Hantaan, Leptospirosa, etc. This dangerous auto-immune epitope must be deleted from Influenza A  vaccine, as well as Dengue 2 vaccine, to avoid enhancing hemorragic auto-antibodies.