Computer analysis of the amino acid sequences in gp41 of apathogenic African green monkey (AGM) virus, less pathogenic HIV-2 and highly pathogenic SIV and HIV-1 lentiviruses.
The bestfit computer program was used to compare the amino acid sequence of the gp160 envelope glycoprotein of an apathogenic AGM and the pathogenic SIVAGM monkey lentiviruses. It was found that the gp120 envelope glycoproteins of these viruses resembled each other in their functional domains. However, an insert of 40 amino acids was found in the gp41 envelope glycoproteins of the pathogenic SIVAGM virus in the amino acid sequence between the membrane anchoring sequence and the carboxyterminus. The insert introduced a new "RRIR" proteolytic cleavage signal into gp41. Comparing HIV-1 gp41 to that of the pathogenic SIVAGM virus revealed that the HIV-1 sequence contains an "RR" sequence that also serves as a signal for proteolytic cleavage. Comparing HIV-2 gp41 to the apathogenic and pathogenic simian immunodeficiency viruses revealed that HIV-2 gp41 lacks the above proteolytic cleavage signal. It is hypothesized that the pathogenic human and simian immunodeficiency lentiviruses can be proteolytically cleaved at the carboxyterminus of gp41, releasing two peptides: a) an "immunodeficiency" 58 amino acid peptide and b) an IL-2-like peptide. The apathogenic AGM virus and the less pathogenic HIV-2 lack one proteolytic cleavage signal in the gp41 amino acid sequence and therefore can release only the IL-2-like peptide but not the "immunodeficiency" peptide. If indeed the pathogenic SIVAGM and HIV-1 do release an "immunodeficiency" peptide, then such a peptide can be regarded as a toxin. Immunization of healthy individuals or HIV-1 patients against the toxic effect of the viral gp41 toxic peptide might prevent damage to the immune system when the virus reactivation leads to ARC and AIDS in infected individuals. Synthetic peptides modeled according to the immunodeficiency peptide (the toxin) can be used to produce anti-toxin antibodies in healthy HIV-1 infected individuals. Such anti-toxin antibodies can be used for passive immunization of AIDS patients or for active immunization of HIV-1 positive individuals prior to ARC or AIDS.
Becker
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Department of Molecular Virology, Faculty of Medicine, Hebrew University of Jerusalem, Israel.
D000595:Amino Acid Sequence; D000818:Animals; D002522:Chlorocebus aethiops / Q000382:microbiology; D006023:Glycoproteins / Q000737:chemistry; D006678:HIV / Q000737:chemistry* / Q000472:pathogenicity; D015700:HIV Envelope Protein gp41 / Q000737:chemistry; D015497:HIV-1 / Q000737:chemistry; D015498:HIV-2 / Q000737:chemistry; D016086:Lentivirus / Q000737:chemistry* / Q000472:pathogenicity; D008969:Molecular Sequence Data; D017421:Sequence Analysis; D017386:Sequence Homology, Amino Acid; D015302:Simian Immunodeficiency Virus / Q000737:chemistry* / Q000472:pathogenicity; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000502:physiology
D006023:Glycoproteins; D015700:HIV Envelope Protein gp41; D014759:Viral Envelope Proteins