Nef mutations in long-term non-progressors from former plasma donors infected with HIV-1 subtype B in China / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To study the specific amino acid variation in Nef that may be related to disease progression after infection with HIV-1 subtype B, a predominant strain circulating in China, and to determine whether changes in Nef secondary structure may influence different stages of AIDS development based on the concept that the Nef gene of HIV infection dramatically alter the severity of viral infection and virus replication and disease progression, and that long-term non-progressors (LTNP) of HIV infection are commonly associated with either a deletion of the Nef gene or the defective Nef alleles.</p><p><b>METHODS</b>The study subjects were divided into LTNP1(n=14), LTNP2 (n=16) and slow progressor (SP, n=19) groups for mutational analysis of the Nef sequence. The data were obtained by using Bioedit, MEGA, Anthewin and SAS software.</p><p><b>RESULTS</b>Residues in Nef TA(48/49) and K151 occurred more frequently in the LTNP group while AA(48/49) was more frequently observed in the SP group. Of the differences observed in the secondary structure comparison using Nef consensus sequences of these three groups, one was roughly corresponding to the Nef(48/49) mutation site.</p><p><b>CONCLUSION</b>TA(48/49), K(151), and AA(48/49) in the Nef gene might be associated with the different stages of HIV infection, and there may be a link between the Nef secondary structure and the progression of HIV-1 infection.</p>

Association between Nef-specific CD8 T-cell responses and disease progression in HIV-1 subtype B infection / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The correlation between HIV-1 Nef-specific CD8 T-cell responses and markers of HIV-1 disease progression still remains unclear. This study analysed and compared the role of HIV-1 Nef-specific CD8 T-cell responses in patients with different disease status.</p><p><b>METHODS</b>Two groups of patients with HIV-1 subtype B infection were selected according to CD4 count and clinical manifestations: long-term nonprogressors (LTNPs, n = 20) and advanced progressors (APs, CD4 count < 500 cells/microl, n = 34). Nef-specific CD8 T-cell responses were studied by interferon-gamma ELISpot assay against 3 pools of HIV-Nef peptides.</p><p><b>RESULTS</b>Nef-specific CD8 T-cell responses did not correlate with viral load or CD4 count in all patients and no significant differences were found in the magnitude of Nef-specific CD8 T-cell responses between groups LTNPs and APs (670 SFC/10(6) peripheral blood mononuclear cells vs 1107 SFC/10(6) peripheral blood mononuclear cells, P = 0.255). Further comparisons showed that there were also no significant correlations observed in group LTNPs, but Nef-specific CD8 T cells correlated negatively with viral load (r = -0.397, P = 0.020) and positively with CD4 count (r = 0.364, P = 0.034) in group APs.</p><p><b>CONCLUSION</b>These data suggest that different correlation patterns between Nef-specific CD8 T-cell responses and disease progression exist in LTNPs and APs. Although a negative association was observed with concurrent plasma HIV RNA in APs, Nef-specific CD8 T-cell responses might fail to play a protective role in different stages of HIV-1 infection.</p>

Biology of the HIV Nef protein.

The accessory Nef protein is expressed by all primate lentiviruses--HIV-1,HIV-2 and simian immune deficiency virus (SIV). Its expression in the early stages of the viral life cycle ensures two basic attributes of HIV infection. These are T-cell activation and the establishment of a persistent state of infection. Nef has a positive effect on viral infection and replication by promoting the survival of infected cells. Its role in HIV persistence is based largely on the ability of Nef to downmodulate the surface levels of important molecules at the immune synapse. These include major histocompatibility complex-I (MHC I) and (MHC II) present on antigen-presenting cells (APCs) and target cells, and CD4 and CD28 present on helper T cells. In this review we present these biological properties of Nef from a mechanistic point of view, and relate them to the structural attributes and interactions of the Nef protein. A brief outline of the limited studies on Nef from Indian subtype C HIV-1 isolates is also presented.

DC-SIGN: binding receptors for hepatitis C virus / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To review the recent developments in and research into binding receptors of hepatitis C virus (HCV) and especially the role of dendritic cell-specific adhesion receptor (DC-SIGN) in HCV.</p><p><b>DATA SOURCES</b>Both Chinese- and English-language literature was searched using MEDLINE (2000 - 2003) and the databank of Chinese-language literature (2000 - 2003).</p><p><b>STUDY SELECTION</b>Relevant articles on DC-SIGN and HCV binding receptors in recent domestic and foreign literature were selected.</p><p><b>DATA EXTRACTION</b>Data were mainly extracted from 40 articles which are listed in the references section of this review.</p><p><b>RESULTS</b>DC-SIGN, a dendritic cell-specific adhesion receptor and a type II transmembrane mannose-binding C-type lectin, is very important in the function of dendritic cells (DC), both in mediating naïve T cell interactions through ICAM-3 and as a rolling receptor that mediates the DC-specific ICAM-2-dependent migration processes. It can be used by HCV and other viral and bacterial pathogens including human immunodeficiency virus (HIV), Ebola virus, CMV and Mycobacterium tuberculosis to facilitate infection. Both DC-SIGN and DC-SIGNR can act either in cis, by concentrating virus on target cells, or in trans, by transmission of bound virus to a target cell expressing appropriate entry receptors. Recent report showed that DC-SIGN not only plays a role in entry into DC, HCV E2 interaction with DC-SIGN might also be detrimental to the interaction of DC with T cells during antigen presentation.</p><p><b>CONCLUSIONS</b>DC-SIGNs are high-affinity binding receptors for HCV. The clinical strategies that target DC-SIGN may be successful in restricting HCV dissemination and pathogenesis as well as directing the migration of DCs to manipulate appropriate immune responses in autoimmunity and tumorigenic situations.</p>

HIV-1 Nef control of cell signalling molecules: multiple strategies to promote virus replication.

HIV-1 has at its disposal numerous proteins encoded by its genome which provide the required arsenal to establish and maintain infection in its host for a considerable number of years. One of the most important and enigmatic of these proteins is Nef. The Nef protein of HIV-1 plays a fundamental role in the virus life cycle. This small protein of approximately 27 kDa is required for maximal virus replication and disease progression. The mechanisms by which it is able to act as a positive factor during virus replication is an area of intense research and although some controversy surrounds Nef much has been gauged as to how it functions. Its ability to modulate the expression of key cellular receptors important for cell activation and control signal transduction elements and events by interacting with numerous cellular kinases and signalling molecules, including members of the Src family kinases, leading to an effect on host cell function is likely to explain at least in part its role during infection and represents a finely tuned mechanism where this protein assists HIV-1 to control its host.