Differential Effects of
            <i>nef</i>
            on HIV Replication: Implications for Viral Pathogenesis in the Host

Cheng‐Mayer, Cecilia; Iannello, Pina; Shaw, Katharina S.; Luciw, Paul A.; Levy, Jay A.

doi:10.1126/science.2531920

Cited by 184 publications

(102 citation statements)

References 22 publications

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“…The most obvious product of the PCR analysis represented nefmRNA. This was surprising in view of the putative role of nef as a factor that negatively regulates viral transcription in some (Fisher et al, 1986;Luciw et al, 1987;Ahmad & Venkatesan, 1988;Cheng-Mayer et al, 1989;Niederman et al, 1989) but not all studies (Kim, 1989b). Using a similar PCR system for detecting spliced HIV-1BaL mRNAs in macrophages (but without conducting a time-course analysis), Robert-Guroff et al (1990) also found a strong nefmRNA signal in macrophages that had been infected with HIV-IBaL for 12 to 14 days.…”

Section: Discussionmentioning

confidence: 99%

Ordered appearance of human immunodeficiency virus type 1 nucleic acids following high multiplicity infection of macrophages

Munis

Kornbluth

Richman

1992

Journal of General Virology

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The order of appearance of human immunodeficiency virus type 1 (HIV-1) nucleic acids was examined in monocyte-derived macrophages following a high multiplicity infection with macrophage-tropic virus. Using the polymerase chain reaction, viral DNA was first detected 2 h after infection and continued to accumulate over the next 24 h. Transcripts representing tat, rev and nefsplicing were detected by 24 h, and transcripts representing env splicing were detected by 48 h after infection. Coincident with the appearance of env transcripts, new synthesis of cellular and extracellular p24 antigen began, multinucleated giant cells formed and progeny infectious virus emerged. This analytical system provides a foundation for further studies on the effects of antiviral agents and cellular factors on the replication cycle of HIV-1 in non-transformed, primary monocyte-derived macrophages.

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Section: Discussionmentioning

confidence: 99%

Ordered appearance of human immunodeficiency virus type 1 nucleic acids following high multiplicity infection of macrophages

Munis

Kornbluth

Richman

1992

Journal of General Virology

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“…The HIV-1 nef gene encodes a protein with an apparent molecular mass of 24-27 kDa, which is myristoylated (Allan et al, 1985;Guy et al, 1987). The biological function of Nef is not yet clear, however, it can be regarded as conclusive that it is not a guanine-nucleotide-binding protein (Kaminchik et al, 1990;Nebreda et al, 1991Nebreda et al, , 1992Matsuura et al, 1991;Backer et al, 1991;Harris et al, 1992;Wolber et al, 1992) participating in cellular signaling pathways as has been claimed by some authors (Samuel et al, 1987;Guy et al, 1987;Cheng-Mayer et al, 1989). Nef is mainly localized in the cytoplasm associated with cellular membranes, but it is also found in the nucleus (Franchini et al, 1986;Kienzle et al, 1992a,b;Ovod et al, 1992;Yu and Felsted, 1992;Kohleisen et al, 1992).…”

mentioning

confidence: 97%

Oligomerization of the Nef protein from human immunodeficiency virus (HIV) type 1

Kienzle

Freund

Kalbitzer

et al. 1993

European Journal of Biochemistry

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The nef genes, derived from two different human immunodeficiency-virus-type-1 (HIV-1) strains, were expressed in procaryotic cells (Escherichia coli) and in eucaryotic cells (insect cells infected with nef-containing baculovirus). The oligomerization of recombinant Nef protein was studied by NMR spectroscopy and immunoblotting under various experimental conditions. 1H-NMR spectroscopy shows that native folded protein has the tendency to polymerize under low-salt conditions. These oligomers become covalently linked by disulfide bonds after decreasing the reduction potential, a process which is fully reversible. Cross-linking studies with bis(sulfo-succinimidyl)suberate and alkylation with iodoacetic acid under non-reducing and reducing conditions document for the first time that Nef can also form homomeric structures including monomers, dimers, trimers and tetramers in cell lysates and intact cells. We found disulfide-linked as well as non-covalently associated oligomers. Since the Nef molecules are not exclusively found in the cytoplasm of HIV infected cells and since the reduced glutathione concentration in lymphocytes of virus infected persons is known to be unusually low, it might be possible that these Nef oligomers have a biological function in vivo as well

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“…It is highly conserved in all primate lentiviruses, suggesting that its function is essential for survival of these pathogens. Nevertheless, early publications reported a negative effect of Nef on viral replication, hence the name 'negative factor' or Nef [93,94]. Subsequent studies, however, demonstrated that Nef plays an important role in several steps of HIV replication.…”

Section: Negative Regulator Factor(nef)mentioning

confidence: 99%

Roles of HIV-1 auxiliary proteins in viral pathogenesis and host-pathogen interactions

Pauza

et al. 2005

Cell Res

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Active host-pathogen interactions take place during infection of human immunodeficiency virus type 1 (HIV-1). Outcomes of these interactions determine the efficiency of viral infection and subsequent disease progression. HIVinfected cells respond to viral invasion with various defensive strategies such as innate, cellular and humoral immune antiviral mechanisms. On the other hand, the virus has also developed various offensive tactics to suppress these host cellular responses. Among many of the viral offensive strategies, HIV-1 viral auxiliary proteins (Tat, Rev, Nef, Vif, Vpr and Vpu) play important roles in the host-pathogen interaction and thus have significant impacts on the outcome of HIV infection. One of the best examples is the interaction of Vif with a host cytidine deaminase APOBEC3G. Although specific roles of other auxiliary proteins are not as well described as Vif-APOBEC3G interaction, it is the goal of this brief review to summarize some of the preliminary findings with the hope to stimulate further discussion and investigation in this exhilarating area of research.

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Differential Effects of nef on HIV Replication: Implications for Viral Pathogenesis in the Host

Cited by 184 publications

References 22 publications

Ordered appearance of human immunodeficiency virus type 1 nucleic acids following high multiplicity infection of macrophages

Ordered appearance of human immunodeficiency virus type 1 nucleic acids following high multiplicity infection of macrophages

Oligomerization of the Nef protein from human immunodeficiency virus (HIV) type 1

Roles of HIV-1 auxiliary proteins in viral pathogenesis and host-pathogen interactions

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