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Effective vaccine development for human immunodeficiency virus type 1 (HIV-1) will require assays that ascertain the capacity of vaccine immunogens to elicit neutralizing antibodies (NAb) to diverse HIV-1 strains. To facilitate NAb assessment in peripheral blood mononuclear cell (PBMC)-based assays, we developed an assay-adaptable platform based on a Renilla luciferase (LucR) expressing HIV-1 proviral...
We earlier reported that immunization of macaques with a reverse transcriptase-deleted SHIV KU2 (ΔrtSHIV KU2 ) plasmid that contained HIV-1(HXB2) env and SIV gag–nef induced protection against AIDS caused by challenge virus SHIV89.6P with a heterologous env. We further deleted vif and integrase from ΔrtSHIV KU2 and substituted the 3′LTR with SV40 poly A sequences, creating...
SHIV deleted in two accessory genes, ΔvpuΔnef SHIV PPC , functioned well as a vaccine against later challenge with highly pathogenic SHIV KU , and it was able to reach the brain after oral inoculation of live virus. In this study, the proviral genome cloned into a plasmid was inoculated as DNA intracerebrally and spread systemically. Few regions of the brain had detectable proviral...
Use of the macaque model of human immunodeficiency virus (HIV) pathogenesis has shown that the accessory genes nef and vpu are important in the pathogenicity of simian immunodeficiency virus (SIV) and simian–human immunodeficiency virus (SHIV). We examined the ability of two nonpathogenic SHIVs, SHIV PPC and ΔvpuΔnefSHIV PPC , to gain pathogenicity by rapid serial passage in macaques...
SHIV KU2 replicates to high levels in inoculated macaques and reproducibly causes an acute depletion of CD4 + T cells. We evaluated the ability of treatment with the antiretroviral drug 9-R-(2-phosphonomethoxypropyl)adenine (PMPA; tenofovir), begun 7 days postinoculation, to inhibit viral replication and associated pathogenesis. Highly productive infection (plasma viral RNA > 10...
The reactivates of human sera with uninduced and phorbol ester (TPA)-induced human herpesvirus-8 (HHV-8)-infected BCBL-1 cells were examined by immunofluorescence assay (IFA) and by radioimmunoprecipitation reactions (RIP). The seroprevalence of HHV-8 infections is low in the United States general population and only low levels of HHV-8 antibodies were detected in the seropositive sera. In contrast,...
RNA–DNA hybrid model substrates which mimic an intermediate of Moloney murine leukemia virus (M-MuLV) reverse transcription at the stage where the tRNA Pro is removed were constructed. This substrate was used to assay the ability of M-MuLV reverse transcriptase (RT) to cleave the RNA portion of the substrate. The cleavage specificities of the cognate M-MuLV RT and the heterologous enzyme from...
Analysis of a limited number of laboratory strains of rabies virus had demonstrated the presence of a genome region bounded by two transcription termination and polyadenylation-like (TTP) signals (approximately 400 to 450 nucleotides apart) which was located between the end of the glycoprotein (G) coding sequence and the beginning of the L polymerase coding sequence. Although this region had been...
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