Prevalence of HCV and HGV infections in Iranian liver transplant recipients.

BACKGROUND: Infections with hepatitis C virus (HCV) and the familially related hepatitis G virus (HGV) threaten survival of liver transplant recipients. The prevalence and pathogenic effects of these hepatitis virus infections, in particular HGV, on clinical outcome and the need for surveillance are controversial. The present study examined the prevalence of HCV and HGV infections using polymerase chain reaction-based molecular methods in Iranian patients who had undergone orthotopic liver transplantation (oLT). MATERIALS AND METHODS: Between 2007 and 2010, 202 EDTA-treated blood samples were obtained before and after liver transplantation in 106 patients. An optimized qualitative in-house multiplex reverse transcription polymerase chain reaction protocol was used for simultaneous diagnosis of HCV and HGV infections. RESULTS: Hepatitis C virus molecular infection was diagnosed in 13 of 202 plasma samples (6.4%) in 10 of 106 patients (9.4%) before and after oLT. Eleven of 202 plasma samples (5.4%) from 10 of 106 patients (9.4%) demonstrated HGV genome infection before and after oLT. CONCLUSION: Detection of moderate prevalence of HCV and especially HGV infection in liver transplant recipients suggests potential importance of HCV infection in liver dysfunction and supports the hypothesis that HGV infection has a pathogenic role in liver-related clinical complications.

Fusion of uninfected T-cells occurs with immature HIV-1 protease-mutant, but not morphologically similar protease inhibitor derived particles.

Protease inhibitors are widely used in the treatment of human immunodeficiency virus type 1 (HIV-1)-infected individuals and show a drastic effect on the reduction of virus load. We previously reported that doughnut-shaped, protease-defective gp120-containing HIV-1 particles from an L-2 cell clone, carrying a provirus with mutations at the pol (protease), env (gp41) and nef genes, rapidly and more effectively induces virus particle-mediated syncytia formation of uninfected T-cells, than a parental wild-type laboratory strain of HIV-1 (LAI). In this study, we examined the possibility of whether enhanced syncytia formation is mediated by morphologically similar doughnut-shaped particles obtained after treatment of LAI-infected cells with the protease inhibitors L-689, 502, DMP-323, RO-31-8959, and KNI-272. Utilizing such protease inhibitor-induced particles and a clone of MOLT-4 cells, we could not detect any enhancement of syncytia formation, over that seen with wild-type LAI particles. This result should alleviate concerns of patients on highly active antiretroviral therapy (HAART), that protease inhibitors might accelerate progression of the disease through enhanced production of defective, 'immature'-appearing particles.

Varied prevalence of Borna disease virus infection in Arabic, thoroughbred and their cross-bred horses in Iran.

Borna disease virus (BDV) naturally infects horses and sheep and induces progressive poliomeningoencephalomyelitis. Here, BDV recombinant proteins of the first open reading frame (ORF-I; coding for p40 nucleoprotein) and the second ORF-II (coding for p24 polymerase cofactor) were immunoblotted with plasma derived from 72 healthy (28 Arabic, 17 thoroughbred and 27 cross-bred) race horses at Tehran in Iran to detect anti-BDV antibodies. In addition, their peripheral blood mononuclear cells (PBMCs) were also examined for BDV RNA by a nested reverse transcriptase-polymerase chain reaction (RT-PCR) at ORF-II. The prevalence of BDV antibodies and/or RNA was 41.2% in Arabic, 23.5% in thoroughbred, and 33.3% in cross-bred horses, but only 17.9, 5.9, and 11.1% of them, respectively, showed positive signals for both BDV antibodies and RNA. Especially, cross-bred horses showed a higher prevalence for BDV RNA, which was detected only in females. In addition, significantly higher prevalence for BDV RNA was observed in Arabic males and thoroughbred females. The BDV prevalence did not increase with aging of the horse. Sequencing at the region of BDV derived from Iranian horses revealed a slight difference from those of Japanese horse- and European horse-derived BDVs even in the amino acid residues, although those in the three groups of Iranian horses were quite similar. Thus, the varied prevalence of BDV was observed with the horse strain or sex in Iranian horses, although BDV sequences were very similar among all three groups in Iran compared with those derived from other countries.

Demonstration of borna disease virus RNA in peripheral blood mononuclear cells derived from domestic cats in Japan.

Borna disease virus (BDV) naturally infects horses, sheep, and several other species, including humans, and it is believed to be related to neurological disorders. BDV infection in domestic cats has also been demonstrated by serological assays. We demonstrated for the first time BDV RNA in peripheral blood mononuclear cells from 11 of 83 (13.3%) randomly selected domestic cats in Japan by nested reverse transcriptase-PCR. The BDVs from cats were similar to but slightly different from those from horses and humans, as shown by sequencing the reverse transcriptase-PCR products. None of the cats was positive for both BDV RNA and anti-BDV antibodies.

Naturally occurring accessory gene mutations lead to persistent human immunodeficiency virus type 1 infection of CD4-positive T cells.

Proviral DNA from cells surviving severe but transient cytopathic effects, mediated by infection with recombinant human immunodeficiency virus type 1 (HIV-1) carrying a single gene mutation at vif, vpr, or vpu, was characterized by use of HIV-1-specific primer pairs in a two-step PCR. Deletion mutations were detected in a region that spanned the vif and vpr open reading frames. Cloning and sequencing of the amplified DNA from this region revealed frequent large deletions in a limited number of nucleotide positions. Analyses of the deletions suggested that (i) genetic recombination, (ii) template-primer slippage, and (iii) misalignment of the growing point during reverse transcription of the HIV-1 genome might be the mechanisms that generated the mutations. Apart from the large deletions, smaller deletions that gave frameshift mutations in vif and/or vpr prevailed. In addition, cells infected with a triple mutant defective in vif, vpr, and vpu did not show any cytopathic effect. Thus, mutations generating multiple accessory gene defects during HIV-1 replication correlate with viral persistence and loss of cytopathogenicity.

Superinfection of a defective human immunodeficiency virus type 1 provirus-carrying T cell clone with vif or vpu mutants gives cytopathic virus particles by homologous recombination.

The partially CD4-expressing T cell clone, Vpr-1, which carries a latent vpr-defective HIV-1 genome and expresses HIV-1 Nef protein only, was permissive to superinfection by HIV-1. Superinfection of Vpr-1 with vif- or vpu-defective mutants, which were noncytopathic, reactivated the vpr-defective virus and led to homologous recombination and cytopathogenesis. The data provide an experimental model for homologous recombination being an important mechanism whereby HIV-1 acquires genetic heterogeneity, and when occurring among defective virus in vivo bestows novel biological activities and virulence.