Genetic and immunological characterization of new subtype G envelope expressing HIV-1 pseudoviruses

• Main Author: Essomba, Rene Ghislain
• Other Authors: Dorfman, Jeffrey
• Format: Doctoral Thesis
• Language: English
• Published: University of Cape Town 2014
• Online Access: http://hdl.handle.net/11427/8705

Includes bibliographical references. === One of the greatest challenges for the development of an effective HIV-1 vaccine is the high genetic diversity of this pathogen and the complex escape mechanisms employed by the envelope gp120 and gp41 glycoprotein that form the envelope spike. An ideal vaccine would elicit the production of broadly neutralizing antibodies (nAb), capable of having potent activity against worldwide viral isolates. This thesis encompasses a series of studies on characterizing the genetic diversity of envelope genes of subtype G and the neutralization antibody responses to these viruses. HIV-1 subtype G accounts for 5% of HIV-1 infection worldwide, centered on West Africa, with spread to European countries, primarily Spain and Portugal, presumably with immigration of infected individuals. Small satellite subtype G epidemics have been documented in Cuba and among Russian intravenous drug users. In addition, 80% of the recombinant strains circulating in Cameroon contain segments attributed to subtype G. However, until recently, little research has been done on the neutralization sensitivity and vulnerabilities of subtype G viruses, particularly those that circulate in its main reservoir, Central and West Africa. We studied plasma derived viruses from eight HIV-1 subtype G infected individuals. Five samples were collected for donation by the Yaoundé Central Hospital Blood Service from individuals who were subsequently found to be HIV-infected. Presumably, these donors were unaware of their HIV status. The remaining three samples were collected at the CIRCB Research Institute in Yaounde during testing for antiretroviral resistance. These donors were failing therapy, and had sufficiently high viral loads that HIV-1 envelope clones could be isolated. The objectives of my thesis were: 1) to examine the molecular and functional characteristics of the HIV-1 envelope glycoproteins of subtype G viral variants which is crucial to improving strategies to prevent transmission; 2) to evaluate the neutralization sensitivity subtype G viruses and the neutralizing capacities of antibodies induced by the viruses by determining the neutralization antibodies titers against autologous and heterologous HIV-1 viral isolates; 3) to characterize the sensitivity of HIV-1 subtype G viral isolates against broadly neutralizing antibodies, to gain insight into the neutralization vulnerabilities of the subtype G viruses.