Disease relevance of HIV-2

• Chemokine receptors and related seven-transmembrane-segment (7TMS) receptors serve as coreceptors for entry of human and simian immunodeficiency viruses (HIV-1, HIV-2, and SIV) into target cells [1].
• Since the HIV-2 promoter has a considerable level of basal expression in the absence of Tat, we constructed a number of modifications in the HIV-2 promoter to minimize the risk of cytotoxicity to cells not containing HIV Tat [2].
• Herein we show that DC-SIGNR, like DC-SIGN, can bind to multiple strains of HIV-1, HIV-2, and simian immunodeficiency virus and transmit these viruses to both T cell lines and human peripheral blood mononuclear cells [3].
• In mouse and human cells infected with HIV-2 tk retroviruses, we show that Tat-induced expression from the HIV-2 promoter results in differential ablation and a massive reduction in Tat-positive cells after ganciclovir treatment [2].
• Active, recombinant p68 reverse transcriptase (RT) from human immunodeficiency virus type 2 (HIV-2), with an NH2-terminal extension containing a hexahistidine sequence was isolated from extracts of Escherichia coli by immobilized metal affinity chromatography [4].

High impact information on HIV-2

• CD4-independent infection by HIV-2 is mediated by fusin/CXCR4 [5].
• Supported by the observation that HIV-2D205 differs in a step of envelope glycoprotein processing, our data indicate that it could represent an alternative HIV-2 subtype and that viruses of the HIV-2/SIVsm/SIVmac group could have already infected humans before HIV-2 and SIVsm/SIVmac diverged [6].
• Furthermore, the proteins of HIV-1 and HIV-2 have different sizes and their serological cross-reactivity is restricted to the major core protein, as the envelope glycoproteins of HIV-2 are not immunoprecipitated by HIV-1-positive sera [7].
• Like CCR5, US28 allowed infection of CD4-positive human cell lines by primary isolates of HIV-1 and HIV-2, as well as fusion of these cell lines with cells expressing the viral envelope proteins [8].
• The compound was active against both HIV-1 and HIV-2 and against 3'-azido-3'-deoxythymidine (AZT)-resistant clinical isolates [9].

Chemical compound and disease context of HIV-2

• Eligible adults (with HIV-1 or HIV-1 and HIV-2 dual seropositivity at stages 2 or 3 of the WHO staging system) received co-trimoxazole chemoprophylaxis (trimethoprim 160 mg, sulphamethoxazole 800 mg) daily or a matching placebo [10].
• The defective replication phenotype was specific for wild-type HIV-1 since HIV-2/SIV isolates, as well as HIV-1 bearing a gag mutation that confers cyclosporin resistance, replicated the same in PPIA(+/+) and PPIA(-/-) cells [11].
• Haloperidol inhibits the HIV-1 and HIV-2 proteases in a concentration-dependent fashion with a Ki of approximately 100 microM [12].
• The crystal structure of HIV-2 protease in complex with a reduced amide inhibitor [BI-LA-398; Phe-Val-Phe-psi (CH2NH)-Leu-Glu-Ile-amide] has been determined at 2.2-A resolution and refined to a crystallographic R factor of 17.6% [13].
• These findings support the use of NRTIs, tenofovir, but not NNRTIs, for treating HIV-2-infected persons or for prophylaxis against HIV-2 and SIV [14].

Biological context of HIV-2

• Nuclear import and cell cycle arrest functions of the HIV-1 Vpr protein are encoded by two separate genes in HIV-2/SIV(SM) [15].
• We have constructed six different combinations of chimeric genes by coupling the truncated HIV-2 gag gene to the neutralizing domain (V3) or the neutralizing and the CD4 binding domains (V3+CD4BD) of gp120 env gene sequences from HIV-1 or HIV-2 [16].
• D-WT does not inhibit cell fusion mediated by the HIV-2 envelope glycoprotein [17].
• Inspection of diverse Nef proteins from HIV-1, HIV-2, and simian immunodeficiency virus revealed a well-conserved sequence in the central region of the C-terminal, solvent-exposed loop of Nef (E/DXXXLphi) that conforms to the consensus sequence of the dileucine-based sorting motifs found in cellular transmembrane proteins [18].
• Mutagenesis of both HIV-1 and HIV-2 Tat demonstrated that the basic domains of both the HIV-1 and HIV-2 Tat proteins were required for this interaction [19].

Anatomical context of HIV-2

• The presence of p27 in the lymphoid cells suppressed replication of some strains of both HIV-1 and HIV-2 [20].
• In contrast, the HIV-2 nef- mutant infected human macrophages as efficiently as the parental virus, whereas viruses lacking the vpr gene either alone or in conjunction with the lack of the nef gene did not replicate in macrophages [21].
• HIV-1 Tat protein is a potent chemoattractant for basophils and lung mast cells obtained from healthy individuals seronegative for Abs to HIV-1 and HIV-2 [22].
• CTL were restimulated with autologous phytohaemagglutinin-stimulated blasts and CTL activities in 'bulk' cultures were evaluated 7 and 14 days later by a standard 51Cr-release assay using autologous B-cell lines infected with recombinant vaccinia expressing HIV-2 Gag, Pol or Nef protein [23].
• ChemR1, an orphan receptor recently shown to bind the CC chemokine I309 (and therefore renamed CCR8), was expressed in monocyte and lymphocyte cell populations and functioned as a coreceptor for diverse HIV-1, HIV-2, and SIV Env proteins [24].

Gene context of HIV-2

• Strains of HIV-2, which are closely related to the SIVs, also often utilise CXCR4, CCR5, BOB and/or Bonzo [25].
• CXCR4 is also a receptor for T-cell-line-adapted, CD4-independent strains of HIV-2 [26].
• Our results show that 10 of 11 HIV-2 isolates were able to efficiently use CCR5 [27].
• Despite broad coreceptor use, the chemokine ligand SDF-1 substantially blocked HIV-2 infectivity of peripheral blood mononuclear cells, indicating that its receptor, CXCR4, was the predominant coreceptor for infection of these cells [28].
• Here we show that a CD4-dependent, T-cell-line-adapted HIV-2 strain uses CXCR4 and, to a lesser extent, CCR3 for fusion with and infectious entry into cells [26].

Analytical, diagnostic and therapeutic context of HIV-2

• Synthetic peptides derived from these conserved domains were used in sensitive and specific immunoassays that detect antibodies in sera from patients infected with HIV-1 or HIV-2 [29].
• HIV-1/HIV-2 enzyme-linked immunosorbent assays, especially those based on env peptides or on the sandwich format, can be negative in HIV-1 subtype O infection [30].
• Furthermore, although the SIVagm vpx proteins are homologous to the HIV-2 group vpx proteins, there are insufficient grounds from sequence analysis for classifying them as vpx proteins [31].
• Metal chelate affinity chromatography has been used to follow reconstitution of the 66- and 51-kDa human immunodeficiency (HIV)-1 and HIV-2 reverse transcriptase (RT) subunits into heterodimer, as well as chimeric enzymes comprised of heterologous subunits [32].
• In electrophoretic mobility shift assays, NF kappa B binds to both conserved sites in the HIV-1 transcriptional enhancer and only to the single conserved site in the HIV-2 transcriptional enhancer [33].

References