Nef from a primary isolate of human immunodeficiency virus type 1 lacking the EE(155) region shows decreased ability to down-regulate CD4.
The human immunodeficiency virus (HIV) nef gene encodes a 27 kDa myristoylated cytosolic protein that has an important role in the pathogenesis of AIDS. One function of Nef is the down-regulation of CD4 and MHC class I surface molecules in HIV-infected cells. Nef directly isolated from an infected individual (KS2), who could be defined as a long-term non-progressor, was compared with Nef from a standard laboratory strain, HIV-1 NL4-3. KS2 Nef protein was characterized by its lowered ability to down-regulate CD4, while still maintaining the ability to down-regulate MHC class I. The ability of KS2 Nef to down-regulate CD4 was more prominent when CD4 was measured 2-3 days after transfer of the nef gene to the target cells, and also when the effect was measured in CD4(+)-enriched primary T cells. The amino acid sequence analysis indicated that the most notable feature of KS2 Nef was lack of the two glutamic acids: the EE(155) region. When the EE(155) region was added to KS2 Nef, the CD4 down-regulation ability was increased almost to the level of NL4-3 Nef. Conversely, when the EE(155) region was deleted from NL4-3, its CD4 down-regulation ability was dramatically impaired. These data suggested that the EE(155) region plays an important role(s) in the down-regulation of CD4 by Nef protein and also that primary nef sequences could be very useful in identifying the original biological functions of Nef in vivo.
Na
Young-Soon
YS
Institute of Molecular Biology and Genetics, Seoul National University, Seoul 151-742, Korea.
Yoon
Keejung
K
Institute of Molecular Biology and Genetics, Seoul National University, Seoul 151-742, Korea.
Nam
Jeong-Gu
JG
Center for AIDS Research, National Institute of Health, Seoul 122-701, Korea.
Choi
Byeongsun
B
Center for AIDS Research, National Institute of Health, Seoul 122-701, Korea.
Lee
Joo-Shil
JS
Center for AIDS Research, National Institute of Health, Seoul 122-701, Korea.
Kato
Ikunoshin
I
TaKaRa-Bio Inc., Seta 3-4-1, Otsu, Shiga, Japan.
Kim
Sunyoung
S
Institute of Molecular Biology and Genetics, Seoul National University, Seoul 151-742, Korea.
D000595:Amino Acid Sequence; D015704:CD4 Antigens / Q000032:analysis*; D015536:Down-Regulation; D015693:Gene Products, nef / Q000737:chemistry* / Q000502:physiology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D013329:Structure-Activity Relationship; D054311:nef Gene Products, Human Immunodeficiency Virus
D015704:CD4 Antigens; D015693:Gene Products, nef; D054311:nef Gene Products, Human Immunodeficiency Virus