PMID- 7903679
OWN - NLM
STAT- MEDLINE
DCOM- 19940202
LR  - 20190508
IS  - 0022-1007 (Print)
IS  - 1540-9538 (Electronic)
IS  - 0022-1007 (Linking)
VI  - 179
IP  - 1
DP  - 1994 Jan 1
TI  - The importance of nef in the induction of human immunodeficiency virus type 1 
      replication from primary quiescent CD4 lymphocytes.
PG  - 115-23
AB  - The viral regulatory gene, nef, is unique to the human immunodeficiency viruses 
      (HIV) and their related primate lentiviruses. Expression of the nef gene has been 
      shown to be essential to the maintenance of high levels of virus replication and 
      the development of pathogenesis in the animal model of simian immunodeficiency 
      virus (SIV) infection. In contrast to this in vivo model, the use of standard T 
      cell culture systems to study nef function in vitro has produced a spectrum of 
      contradictory results, and has failed to demonstrate a significant positive 
      influence of nef on viral life cycle. We have developed a cell model to study 
      regulation of HIV-1 replication that we believe reflects more accurately 
      virus-cell interactions as they occur in vivo. Our experimental system used acute 
      virus infection of purified, quiescent CD4 lymphocytes and subsequent induction 
      of viral replication through T cell activation. With this cell model, NL4-3 virus 
      clones with open and mutated nef reading frames were compared for replication 
      competence. The clones with nef mutations showed reproducible and significant 
      reductions in both rates of growth and maximal titers achieved. The degree of 
      reduced replication was dependent on initial virus inoculum and the timing of T 
      cell activation. The influence of nef was highly significant for induction of 
      virus replication from a latent state within resting CD4 cells. Its effect was 
      less apparent for virus infection of fully proliferating CD4 cells. This study 
      demonstrates that nef confers a positive growth advantage to HIV-1 that becomes 
      readily discernable in the primary cell setting of virus induction through T cell 
      activation. The experimental cell model, which we describe here, provides not 
      only a means to study nef function in vitro, but also provides important clues to 
      the function of nef in HIV infection in vivo.
FAU - Spina, C A
AU  - Spina CA
AD  - Department of Pathology, University of California San Diego, La Jolla 92093-0679.
FAU - Kwoh, T J
AU  - Kwoh TJ
FAU - Chowers, M Y
AU  - Chowers MY
FAU - Guatelli, J C
AU  - Guatelli JC
FAU - Richman, D D
AU  - Richman DD
LA  - eng
GR  - AI-27670/AI/NIAID NIH HHS/United States
GR  - AI-29164/AI/NIAID NIH HHS/United States
GR  - AI-57578/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Exp Med
JT  - The Journal of experimental medicine
JID - 2985109R
RN  - 0 (DNA Primers)
SB  - IM
GS  - nef
MH  - Base Sequence
MH  - CD4-Positive T-Lymphocytes/*microbiology
MH  - Cells, Cultured
MH  - DNA Primers
MH  - *Genes, nef
MH  - HIV-1/*physiology
MH  - Humans
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Virus Replication/*genetics
PMC - PMC2191324
EDAT- 1994/01/01 00:00
MHDA- 1994/01/01 00:01
PMCR- 1994/07/01
CRDT- 1994/01/01 00:00
PHST- 1994/01/01 00:00 [pubmed]
PHST- 1994/01/01 00:01 [medline]
PHST- 1994/01/01 00:00 [entrez]
PHST- 1994/07/01 00:00 [pmc-release]
AID - 94095917 [pii]
AID - 10.1084/jem.179.1.115 [doi]
PST - ppublish
SO  - J Exp Med. 1994 Jan 1;179(1):115-23. doi: 10.1084/jem.179.1.115.