Current Clinical Microbiology Reports最新文献

Purpose of review: This review focuses specifically on the mechanisms by which female sex hormones, estrogen and progesterone, affect Chlamydia trachomatis infections in vivo and in vitro.

Recent findings: Recent data support previous work indicating that estrogen enhances chlamydial development via multiple mechanisms. Progesterone negatively impacts Chlamydia infections also through multiple mechanisms, particularly by altering the immune response. Conflicting data exist regarding the effect of synthetic hormones, such as those found in hormonal contraceptives, on chlamydial infections.

Summary: Numerous studies over the years have indicated that female sex hormones affect C. trachomatis infection. However, we still do not have a clear understanding of how these hormones alter Chlamydia disease transmission and progression. The studies reviewed here indicate that there are many variables that determine the outcome of Chlamydia/hormone interactions, including: 1) the specific hormone, 2) hormone concentration, 3) cell type or area of the genital tract, 4) hormone responsiveness of cell lines, and 5) animal models.

Purpose of review: Communication by epithelial cells during respiratory viral infections is critical in orchestrating effective anti-viral responses but also can lead to excessive inflammation. This review will evaluate studies that investigate how respiratory epithelial cells influence the behavior of immune cells and how epithelial cell/immune cell interactions contribute to antiviral responses and immunopathology outcomes.

Recent findings: Previous studies have characterized cytokine responses of virus-infected epithelial cells. More recent studies have carefully demonstrated the effects of these cytokines on cellular behaviors within the infected lung. Infected epithelial cells release exosomes that specifically regulate responses of monocytes and neighboring epithelial cells without promoting spread of virus. In contrast, rhinovirus-infected cells induce monocytes to upregulate expression of the viral receptor, promoting spread of the virus to alternate cell types. The precise alteration of PDL expression on infected epithelial cells has been shown to switch between inhibition and activation of antiviral responses.

Summary: These studies have more precisely defined the interactions between epithelial and immune cells during viral infections. This level of understanding is critical for the development of novel therapeutic strategies that promote effective antiviral responses or epithelial repair, or inhibit damaging inflammatory responses during severe respiratory viral infections.

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.

Purpose of this review: Human gammaherpesviruses have complex lifecycles that drive their pathogenesis. KSHV and EBV are the etiological agents of multiple cancers worldwide. There is no FDA-approved vaccine for either KSHV or EBV. This review will describe recent progress in understanding EBV and KSHV lifecycles during infection.

Recent findings: Determining how latency is established, particularly how non-coding RNAs influence latent and lytic infection, is a rapidly growing area of investigation into how gammaherpesviruses successfully persist in the human population. Many factors have been identified as restrictors of reactivation from latency, especially innate immune antagonism. Finally, new host proteins that play a role in lytic replication have been identified.

Summary: In this review we discuss recent findings over the last 5 years on both host and viral factors that are involved in EBV and KSHV pathogenesis.

Purpose of review: Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 and is listed in the World Health Organization's blueprint of priority diseases that need immediate research. Camels are reservoirs of this virus, and the virus spills over into humans through direct contact with camels. Human-to-human transmission and travel-associated cases have been identified as well. Limited studies have characterized the molecular pathogenesis of MERS-CoV. Most studies have used ectopic expression of viral proteins to characterize MERS-CoV and its ability to modulate antiviral responses in human cells. Studies with live virus are limited, largely due to the requirement of high containment laboratories. In this review, we have summarized current studies on MERS-CoV molecular pathogenesis and have mentioned some recent strategies that are being developed to control MERS-CoV infection.

Recent findings: Multiple antiviral molecules with the potential to inhibit MERS-CoV infection by disrupting virus-receptor interactions are being developed and tested. Although human vaccine candidates are still being developed, a candidate camel vaccine is being tested for efficacy. Combination of supportive treatment with interferon and antivirals is also being explored.

Summary: New antiviral molecules that inhibit MERS-CoV and host cell receptor interaction may become available in the future. Additional studies are required to identify and characterize the pathogenesis of MERS-CoV EMC/2012 and other circulating strains. An effective MERS-CoV vaccine, for humans and/or camels, along with an efficient combination antiviral therapy may help us prevent future MERS cases.

Purpose of review: Entamoeba histolytica is a protozoan parasite that causes amebiasis, which remains a significant cause of morbidity and mortality worldwide. E. histolytica causes tissue destruction which leads to clinical disease. This review outlines some of the recent advances that have furthered our understanding of the processes that lead to the tissue damage caused by E. histolytica.

Recent findings: Recent studies have identified new mechanisms involved in E. histolytica-induced tissue damage. These include (i) new form of contact-dependent killing called trogocytosis; (ii) parasite-produced cytokine, macrophage migration inhibitory factor, that contributes to inflammation; (iii) exploitation of host immune response to promote invasion; and (iv) the contribution of the gut microbiome to clinical disease.

Summary: Targeting these mechanisms that result in tissue injury should be a focus of future research for the development of improved preventive and therapeutic strategies for amebiasis.

Purpose of review: Kaposi's sarcoma-associated herpesvirus (KSHV), the etiological agent of the AIDS-associated tumor Kaposi's sarcoma, is a complex virus that expresses ~90 proteins in a regulated temporal cascade during its replication cycle. Although KSHV relies on cellular machinery for gene expression, it also uses specialized regulators to control nearly every step of the process. In this review we discuss the current understanding of KSHV gene regulation.

Recent findings: High-throughput sequencing and a new robust system to mutate KSHV have paved the way for comprehensive studies of KSHV gene expression, leading to the characterization of new viral factors that control late gene expression and post-transcriptional steps of gene regulation. They have also revealed key aspects of chromatin-based control of gene expression in the latent and lytic cycle.

Summary: The combination of mutant analysis and high-throughput sequencing will continue to expand our model of KSHV gene regulation and point to potential new targets for anti-KSHV drugs.

Purpose of review: Interferon-induced transmembrane protein 3 (IFITM3) is a cellular restriction factor that blocks fusion between virus and host membranes. Here, we provide an introduction to IFITM3 and the biochemical regulation underlying its antiviral activity. Further, we analyze and summarize the published literature examining phenotypes of IFITM3 knockout mice upon infections with viral pathogens and discuss the controversial association between single nucleotide polymorphisms (SNPs) in the human IFITM3 gene and severe virus infections.

Recent findings: Recent publications show that IFITM3 knockout mice experience more severe pathologies than wild-type mice in diverse virus infections, including infections with influenza A virus, West Nile virus, Chikungunya virus, Venezuelan equine encephalitis virus, respiratory syncytial virus, and cytomegalovirus. Likewise, numerous studies of humans of Chinese ancestry have associated the IFITM3 SNP rs12252-C with severe influenza virus infections, though examinations of other populations, such as Europeans, in which this SNP is rare, have largely failed to identify an association with severe infections. A second SNP, rs34481144-A, found in the human IFITM3 promoter has also recently been reported to be a risk allele for severe influenza virus infections.

Summary: There is significant evidence for a protective role of IFITM3 against virus infections in both mice and humans, though additional work is required to identify the range of pathogens restricted by IFITM3 and the mechanisms by which human SNPs affect IFITM3 levels or functionality.