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Family Birnaviridae
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
Next, Martinez-Torrecuadrada et al. (2000b) expressed the VPX, defined in Figure 14.1 and known now as pVP2, VP2, and VP3, singly or in different combinations, in the baculovirus expression system. The VPX, or pVP2, and especially VP3 were expressed at high levels and were simple to purify. The immunogenicity of both proteins was like that of the native virus, while the VPX was able to elicit neutralizing antibodies, but the VP3 was not. The authors found that the VPX protein formed tubule-like structures, where the capsomer structure was very similar if not identical to that within the virions, while VP3 did not form any particles.
HIV-2
Published in Niel T. Constantine, Johnny D. Callahan, Douglas M. Watts, Retroviral Testing, 2020
Niel T. Constantine, Johnny D. Callahan, Douglas M. Watts
The major regulatory genes tat and rev appear analogous in HIV-1 and HIV-2, although they may vary more in the HIV-2 virus. However, one of the regulatory components, vpx (pl6), is present in HIV-2 but not in HIV-1; it is similar in function to the vpu of HIV-1, may be responsible for determining which cells are infected with the virus, and may be responsible for the different pathologic effects noted with HIV-2 infection. Antibody responses to vpx have been detected in about 14% of HIV-2-infected individuals. This may have important diagnostic application, since the detection of antibodies to vpx will identify HIV-2 infection, especially when sera react by both assays. Antibodies to the nef regulatory protein, which may not function as a down regulator in HIV-2, have been detected in about 25% of HIV-2-infected individuals. Sera that contain HIV-1 antibodies have no neutralizing affect on HIV-2 isolates, which contrasts with the cross-neutralizing activity of HIV-2 sera on HIV-1 isolates.
SAMHD1: Recurring roles in cell cycle, viral restriction, cancer, and innate immunity
Published in Autoimmunity, 2018
Christopher H. Mauney, Thomas Hollis
SAMHD1 has garnered significant attention for its antiviral properties in non-dividing cells of hematopoietic lineage, including macrophages, dendritic cells, and resting CD4 + T-cells [141,142,143]. In these cells, it is constitutively expressed and present in the dephosphorylated state, where it contributes to the maintenance of dNTP levels that are several 100-fold lower than in actively cycling CD4 + T-cells [164]. Interestingly, the presence of dephosphorylated SAMHD1 in these cells coincides with the capacity of non-dividing hematopoietic cells to restrict efficient HIV-1 infection [101,145–148]. HIV-2 however, which carries the virulence accessory protein, Vpx, is able to efficiently transduce non-dividing hematopoietic cells. Incorporation of Vpx into HIV-1 virions relieved the restrictive phenotype and suggested the presence of a specific cellular immune factor antagonized by Vpx [141,142,149].
The potential of the CMB305 vaccine regimen to target NY-ESO-1 and improve outcomes for synovial sarcoma and myxoid/round cell liposarcoma patients
Published in Expert Review of Vaccines, 2018
DC-SIGN (CD209) is a cell surface C-type lectin-like protein highly specific for immature DCs that acts as a scavenger receptor enabling lentiviral infection [32]. The alpha virus Sindbis also infects DC by using DC-SIGN as an attachment receptor, but has a broader tropism due to its affinity for ubiquitously expressed heparan sulfate [33]. Through selective mutation of the heparin binding region, a Sindbis envelope was genetically engineered that selectively binds to DC-SIGN [33,34]. ‘ZVex’ is a novel vector platform for DC-targeted vaccines that is built on a third-generation LV and includes a DC-SIGN tropic Sindbis Virus envelope (Figure 1(a)). Like other third-generation LVs generally regarded as safe for use in gene therapy, ZVex is devoid of all HIV 1-derived accessory proteins, except for Rev, and is encoded by a split genome with a deletion in the U3 region (ΔU3, for self-inactivation of the 3ʹLTR). The ΔU3 deletion is a self-inactivating mutation that: (1) prevents transcription of the full-length vector genome (vg) from reversed transcribed dsDNA vectors in the infected target cell, and (2) minimizes the risk of insertional activation that can occur when a 3ʹLTR can function as a promoter after integration. In addition, ZVex contains the Vpx protein (viral protein X from simian immune deficiency virus [SIV]) that is packaged into the vector particles and overcomes the HIV-restriction factor SAMHD1 in DC, which depletes the nucleotide triphosphate pool, thereby preventing reverse transcription of the vg. Further important safety features of ZVex are a genetically modified capsid gene to reduce the risk of recombination, and a genetically inactivated integrase enzyme (D64V mutation), which significantly reduces the risk of integration (Figure 1(b)) [35].