Reovirus: Friend and Foe.

PURPOSE OF REVIEW: Mammalian orthoreovirus (reovirus) is a powerful tool for studying viral replication and pathogenesis. Most reovirus infections are subclinical, however recent work has catapulted reovirus into the clinical spotlight. RECENT FINDINGS: Owing to its capacity to kill cancer cells more efficiently than normal cells, reovirus is under development as a therapeutic for a variety of cancers. New efforts have focused on genetically engineering reovirus to increase its oncolytic capacity, and determining how reovirus potentiates immunotherapy. Other recent studies highlight a potential role for reovirus in celiac disease (CeD). Using mouse models of CeD, reovirus caused loss of oral tolerance to dietary antigens, opening the possibility that reovirus could trigger CeD in humans. SUMMARY: We will focus on new developments in reovirus oncolysis and studies suggesting a role for reovirus as a trigger for celiac disease (CeD) that make reovirus a potential friend and foe to human health.

Host and pathogen interface: microRNAs are modulators of disease outcome.

Chlamydiae are a group of intracellular bacterium that infect a range of hosts and are responsible for the most common sexual transmitted infections, which could be the result of a plethora of factors leading to varied pathological outcomes. This review aims to show that Chlamydia possibly manipulates host defenses through microRNAs interaction.

MicroRNAs Modulate Pathogenesis Resulting from Chlamydial Infection in Mice.

Not all women infected with chlamydiae develop upper genital tract disease, but the reason(s) for this remains undefined. Host genetics and hormonal changes associated with the menstrual cycle are possible explanations for variable infection outcomes. It is also possible that disease severity depends on the virulence of the chlamydial inoculum. It is likely that the inoculum contains multiple genetic variants, differing in virulence. If the virulent variants dominate, then the individual is more likely to develop severe disease. Based on our previous studies, we hypothesized that the relative degree of virulence of a chlamydial population dictates the microRNA (miRNA) expression profile of the host, which, in turn, through regulation of the host inflammatory response, determines disease severity. Thus, we infected C57BL/6 mice with two populations of Chlamydia muridarum, each comprised of multiple genetic variants and differing in virulence: an attenuated strain (NiggA) and a virulent strain (NiggV). NiggA and NiggV elicited upper tract pathology in 54% and 91% of mice, respectively. miRNA expression analysis in NiggV-infected mice showed significant downregulation of miRNAs involved in dampening fibrosis (miR-200b, miR-200b-5p, and 200b-3p miR-200a-3p) and in transcriptional regulation of cytokine responses (miR-148a-3p, miR-152-3p, miR-132, and miR-212) and upregulation of profibrotic miRNAs (miR-142, and miR-147). Downregulated miRNAs were associated with increased expression of interleukin 8 (IL-8), CXCL2, IL-1ß, tumor necrosis factor alpha (TNF-α), and IL-6. Infection with NiggV but not NiggA led to decreased expression of Dicer and Ago 2, suggesting that NiggV interaction with host cells inhibits expression of the miRNA biogenesis machinery, leading to increased cytokine expression and pathology.