title: Matrix and envelope coevolution revealed in a patient monitored since primary infection with human immunodeficiency virus type 1.
abstract: Lentiviruses, including human immunodeficiency virus type 1 (HIV-1), typically encode envelope glycoproteins (Env) with long cytoplasmic tails (CTs). The strong conservation of CT length in primary isolates of HIV-1 suggests that this factor plays a key role in viral replication and persistence in infected patients. However, we report here the emergence and dominance of a primary HIV-1 variant carrying a natural 20-amino-acid truncation of the CT in vivo. We demonstrated that this truncation was deleterious for viral replication in cell culture. We then identified a compensatory amino acid substitution in the matrix protein that reversed the negative effects of CT truncation. The loss or rescue of infectivity depended on the level of Env incorporation into virus particles. Interestingly, we found that a virus mutant with defective Env incorporation was able to spread by cell-to-cell transfer. The effects on viral infectivity of compensation between the CT and the matrix protein have been suggested by in vitro studies based on T-cell laboratory-adapted virus mutants, but we provide here the first demonstration of the natural occurrence of similar mechanisms in an infected patient. Our findings provide insight into the potential of HIV-1 to evolve in vivo and its ability to overcome major structural alterations.
authors.affiliation: Université François Rabelais, Tours, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Beaumont
authors.forename: Daniela
authors.initials: D
authors.lastname: Vendrame
authors.forename: Bernard
authors.initials: B
authors.lastname: Verrier
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Roch
authors.forename: François
authors.initials: F
authors.lastname: Biron
authors.forename: Françis
authors.initials: F
authors.lastname: Barin
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Mammano
authors.forename: Denys
authors.initials: D
authors.lastname: Brand
mesh_terms: D000595:Amino Acid Sequence; D003593:Cytoplasm / Q000821:virology; D005434:Flow Cytometry / Q000379:methods; D015686:Gene Products, env / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D018613:Microscopy, Confocal / Q000379:methods; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D017386:Sequence Homology, Amino Acid; D019562:Viral Load; D014779:Virus Replication
chemical_list: D015686:Gene Products, env