Matrix and envelope coevolution revealed in a patient monitored since primary infection with human immunodeficiency virus type 1.
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.
Beaumont
Elodie
E
Université François Rabelais, Tours, France.
Vendrame
Daniela
D
Verrier
Bernard
B
Roch
Emmanuelle
E
Biron
François
F
Barin
Françis
F
Mammano
Fabrizio
F
Brand
Denys
D
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
D015686:Gene Products, env