A peptide-loaded dendritic cell based cytotoxic T-lymphocyte (CTL) vaccination strategy using peptides that span SIV Tat, Rev, and Env overlapping reading frames

CTL based vaccine strategies in the macaque model of AIDS have shown promise in slowing the progression to disease. However, rapid CTL escape viruses can emerge rendering such vaccination useless. We hypothesized that such escape is made more difficult if the immunizing CTL epitope falls within a region of the virus that has a high density of overlapping reading frames which encode several viral proteins. To test this hypothesis, we immunized macaques using a peptide-loaded dendritic cell approach employing epitopes in the second coding exon of SIV Tat which spans reading frames for both Env and Rev. We report here that autologous dendritic cells, loaded with SIV peptides from Tat, Rev, and Env, induced a distinct cellular immune response measurable ex vivo. However, conclusive in vivo control of a challenge inoculation of SIVmac239 was not observed suggesting that CTL epitopes within densely overlapping reading frames are also subject to escape mutations

Zika Fetal Neuropathogenesis: Etiology of a Viral Syndrome

The ongoing Zika virus epidemic in the Americas and the observed association with both fetal abnormalities (primary microcephaly) and adult autoimmune pathology (Guillain–Barré syndrome) has brought attention to this neglected pathogen. While initial case studies generated significant interest in the Zika virus outbreak, larger prospective epidemiology and basic virology studies examining the mechanisms of Zika viral infection and associated pathophysiology are only now starting to be published. In this review, we analyze Zika fetal neuropathogenesis from a comparative pathology perspective, using the historic metaphor of “TORCH” viral pathogenesis to provide context. By drawing parallels to other viral infections of the fetus, we identify common themes and mechanisms that may illuminate the observed pathology. The existing data on the susceptibility of various cells to both Zika and other flavivirus infections are summarized. Finally, we highlight relevant aspects of the known molecular mechanisms of flavivirus replication

Retrovirus infected cells contain viral microRNAs

<p>Abstract</p> <p>The encoding of microRNAs in retroviral genomes has remained a controversial hypothesis despite significant supporting evidence in recent years. A recent publication demonstrating the production of functional miRNAs from the retrovirus bovine leukemia virus adds further credence to the fact that retroviruses do indeed encode their own miRNAs. Here we comment on the importance of this paper to the field, as well as examine the other known examples of miRNAs encoded by RNA viruses.</p

Expression of ZIKV receptors in human brain and placental tissue.

<p>NA = data not available.</p

Alignment of first 130 nucleotides of 3’UTR of ZIKV, illustrating Musashi binding element (MBE) location and associated mutations over time and geographic spread.

<p>Sequences shown are the only ones that are unique for country and/or sequence; duplicates of the same country were discarded. Alignment was performed using the MAFFT multiple sequence alignment program for unix-like operating systems. Visualization was performed using Geneious. There is presence of stem-loop I (SL I) and stem-loop II (SL II) on those sequences, with SL II being partially shown. There is also presence of MBE on SL II, with two SNPs on African sequences, which could potentially change the RNA structure and availability of the element. SL I and SL II were annotated from Zhu Z. et al. MBE was annotated using the UTRscan tool of UTRSite (<a href="http://utrsite.ba.itb.cnr.it/" target="_blank">http://utrsite.ba.itb.cnr.it/</a>).</p

IL-21 and Probiotic Therapy Improve TH17 Frequencies, Microbial Translocation, and Microbiome in ARV-Treated, SIV-Infected Macaques

Increased mortality in antiretroviral (ARV)-treated, HIV-infected individuals has been attributed to persistent immune dysfunction, in part due to abnormalities at the gastrointestinal barrier. In particular, the poor reconstitution of gastrointestinal T H 17 cells correlates with residual translocation of dysbiotic, immunostimulatory microflora across a compromised intestinal epithelial barrier. We have previously demonstrated that oral probiotics promote increased intestinal CD4+ T-cell reconstitution during ARV treatment in a non-human primate model of HIV infection; however, essential mucosal T-cell subsets, such as T H 17 cells, had limited recovery. Here, we sought to promote T H 17 cell recovery by administering IL-21 to a limited number of ARV-treated, probiotic-supplemented, SIV-infected pigtailed macaques. We demonstrate that probiotic and IL-21 supplementation of ARVs is associated with enhanced polyfunctional T H 17 expansion and reduced markers of microbial translocation and dysbiosis as compared to infected controls receiving ARVs alone. Importantly, treatment resulted in fewer morbidities compared to controls, and was independent of increased immune activation or loss of viral suppression. We propose that combining ARVs with therapeutics aimed at restoring intestinal stasis may significantly improve disease prognosis of ARV-treated, HIV-infected, individuals