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Evidence for a continuous drift of the HIV-1 species towards higher resistance to neutralizing antibodies over the course of the epidemic.
- Source :
-
PLoS pathogens [PLoS Pathog] 2013; Vol. 9 (7), pp. e1003477. Date of Electronic Publication: 2013 Jul 04. - Publication Year :
- 2013
-
Abstract
- We compared the neutralization sensitivity of early/transmitted HIV-1 variants from patients infected by subtype B viruses at 3 periods of the epidemic (1987-1991, 1996-2000, 2006-2010). Infectious pseudotyped viruses expressing envelope glycoproteins representative of the viral quasi-species infecting each patient were tested for sensitivity to neutralization by pools of sera from HIV-1 chronically infected patients and by an updated panel of 13 human monoclonal neutralizing antibodies (HuMoNAbs). A progressive significantly enhanced resistance to neutralization was observed over calendar time, by both human sera and most of the HuMoNAbs tested (b12, VRC01, VRC03, NIH45-46(G54W), PG9, PG16, PGT121, PGT128, PGT145). Despite this evolution, a combination of two HuMoNAbs (NIH45-46(G54W) and PGT128) still would efficiently neutralize the most contemporary transmitted variants. In addition, we observed a significant reduction of the heterologous neutralizing activity of sera from individuals infected most recently (2003-2007) compared to patients infected earlier (1987-1991), suggesting that the increasing resistance of the HIV species to neutralization over time coincided with a decreased immunogenicity. These data provide evidence for an ongoing adaptation of the HIV-1 species to the humoral immunity of the human population, which may add an additional obstacle to the design of an efficient HIV-1 vaccine.
- Subjects :
- Antibodies, Monoclonal metabolism
Antibody Specificity
Antigens, Viral biosynthesis
Antigens, Viral genetics
Antigens, Viral metabolism
Cohort Studies
Epidemiological Monitoring
Epitopes genetics
France epidemiology
HIV Infections epidemiology
HIV Infections transmission
HIV-1 genetics
HIV-1 metabolism
Humans
Immunity, Humoral
Immunogenetic Phenomena
Membrane Glycoproteins antagonists & inhibitors
Membrane Glycoproteins genetics
Membrane Glycoproteins metabolism
Phylogeny
RNA, Viral blood
RNA, Viral metabolism
Viral Envelope Proteins antagonists & inhibitors
Viral Envelope Proteins genetics
Viral Envelope Proteins metabolism
Antibodies, Neutralizing metabolism
Epidemics
Genetic Drift
HIV Infections immunology
HIV Infections virology
HIV-1 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1553-7374
- Volume :
- 9
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- PLoS pathogens
- Publication Type :
- Academic Journal
- Accession number :
- 23853594
- Full Text :
- https://doi.org/10.1371/journal.ppat.1003477