Open AccessModulation of Different Human Immunodeficiency Virus Type 1 Nef Functions during Progression to AIDS
Author(s) -
Silke Carl,
Thomas C. Greenough,
Mandy Krumbiegel,
Michael E. Greenberg,
Jacek Skowroński,
John L. Sullivan,
Frank Kirchhoff
Publication year - 2001
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.75.8.3657-3665.2001
Subject(s) - biology , virology , viral replication , infectivity , virus , downregulation and upregulation , pathogenesis , major histocompatibility complex , immunology , disease , viral pathogenesis , gene , immune system , genetics , medicine , pathology
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.