Modulation of different human immunodeficiency virus type 1 Nef functions during progression to AIDS.
The human immunodeficiency virus type 1 (HIV-1) Nef protein has several independent functions that might contribute to efficient viral replication in vivo. Since HIV-1 adapts rapidly to its host environment, we investigated if different Nef properties are associated with disease progression. Functional analysis revealed that nef alleles obtained during late stages of infection did not efficiently downmodulate class I major histocompatibility complex but were highly active in the stimulation of viral replication. In comparison, functional activity in downregulation of CD4 and enhancement of HIV-1 infectivity were maintained or enhanced after AIDS progression. Our results demonstrate that various Nef activities are modulated during the course of HIV-1 infection to maintain high viral loads at different stages of disease progression. These findings suggest that all in vitro Nef functions investigated contribute to AIDS pathogenesis and indicate that nef variants with increased pathogenicity emerge in a significant number of HIV-1-infected individuals.
Carl
S
S
Institute for Clinical and Molecular Virology, Friedrich-Alexander University, D-91054 Erlangen, Germany.
Greenough
T C
TC
Krumbiegel
M
M
Greenberg
M
M
Skowronski
J
J
Sullivan
J L
JL
Kirchhoff
F
F
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D000483:Alleles; D015704:CD4 Antigens / Q000378:metabolism; D002460:Cell Line; D015331:Cohort Studies; D016384:Consensus Sequence / Q000235:genetics; D018450:Disease Progression; D015536:Down-Regulation; D015693:Gene Products, nef / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D008954:Models, Biological; D013997:Time Factors; D017735:Virus Latency; D014779:Virus Replication; D054311:nef Gene Products, Human Immunodeficiency Virus
D015704:CD4 Antigens; D015693:Gene Products, nef; D015395:Histocompatibility Antigens Class I; D054311:nef Gene Products, Human Immunodeficiency Virus