Current Clinical Microbiology Reports最新文献

Purpose of the review: Immunotherapy has emerged as a promising cancer treatment, however success in only select clinical indications underscores the need for novel approaches. Recently Listeria monocytogenes-based vaccines have been developed to drive tumor specific T-cell responses. Here, we discuss recent preclinical studies using L. monocytogenes vaccines, innate immune pathways that influence T-cell priming, and new vaccine strategies in clinical trials.

Recent findings: Recent studies indicate that in addition to inducing antigen specific T-cell responses, L. monocytogenes vaccines remodel the TME. In addition, several innate immune pathways influence adaptive immune responses to L. monocytogenes and modulating these pathways holds promise to enhance anti-tumor T-cell responses.

Summary: The interplay between innate and adaptive immune responses to L. monocytogenes is poorly understood. Understanding these interactions will facilitate the design of better anti-cancer vaccines and improved use of combination therapies.

Purpose of review: Neonatal infection by herpes simplex virus (HSV) 1 or 2 presents a devastating burden to new parents, due to the unpredictability of severe clinical outcomes, as well as the potential for lifelong reactivation. While just under half of neonatal HSV infections have mild clinical impacts akin to those observed in adults, the other half experience viral spread throughout the body (disseminated infection) and/or the brain (central nervous system infection).

Summary: Here we summarize current data on clinical diagnostic measures, antiviral therapy, and known factors of human host biology that contribute to the distinct neonatal outcomes of HSV infection.

Recent findings: We then explore recent new data on how viral genetic diversity between infections may impact clinical outcomes. Further research will be critical to build upon these early findings and to provide statistical power to our ability to discern and/or predict the potential clinical path of a given neonatal infection.

Purpose of review: The design of novel herpes simplex type I (HSV-1)-derived oncolytic virotherapies is a balancing act between safety, immunogenicity and replicative potential. We have undertaken this review to better understand how these considerations can be incorporated into rational approaches to the design of novel herpesvirus oncolytic virotherapies.

Recent findings: Several recent papers have demonstrated that enhancing the potential of HSV-1 oncolytic viruses to combat anti-viral mechanisms present in the tumor microenvironment leads to greater efficacy than their parental viruses.

Summary: It is not entirely clear how the immunosuppressive tumor microenvironment affects oncolytic viral replication and spread within tumors. Recent work has shown that the manipulation of specific cellular and molecular mechanisms of immunosuppression operating within the tumor microenvironment can enhance the efficacy of oncolytic virotherapy. We anticipate that future work will integrate greater knowledge of immunosuppression in tumor microenvironments with design of oncolytic virotherapies.

Purpose of review: Varicella zoster virus (VZV) is a highly contagious, neurotropic alpha herpes virus that causes varicella (chickenpox). VZV establishes lifelong latency in the sensory ganglia from which it can reactivate to induce herpes zoster (HZ), a painful disease that primarily affects older individuals and those who are immune-suppressed. Given that VZV infection is highly specific to humans, developing a reliable in vivo model that recapitulates the hallmarks of VZV infection has been challenging. Simian Varicella Virus (SVV) infection in nonhuman primates reproduces the cardinal features of VZV infections in humans and allows the study of varicella virus pathogenesis in the natural host. In this review, we summarize our current knowledge about genomic and virion structure of varicelloviruses as well as viral pathogenesis and antiviral immune responses during acute infection, latency and reactivation. We also examine the immune evasion mechanisms developed by varicelloviruses to escape the host immune responses and the current vaccines available for protecting individuals against chickenpox and herpes zoster.

Recent findings: Data from recent studies suggest that infected T cells are important for viral dissemination to the cutaneous sites of infection as well as site of latency and that a viral latency-associated transcript might play a role in the transition from lytic infection to latency and then reactivation.

Summary: Recent studies have provided exciting insights into mechanisms of varicelloviruses pathogenesis such as the critical role of T cells in VZV/SVV dissemination from the respiratory mucosa to the skin and the sensory ganglia; the ability of VZV/SVV to interfere with host defense; and the identification of VLT transcripts in latently infected ganglia. However, our understanding of these phenomena remains poorly understood. Therefore, it is critical that we continue to investigate host-pathogen interactions during varicelloviruses infection. These studies will lead to a deeper understanding of VZV biology as well as novel aspects of cell biology.

Purpose of review: Epstein-Barr virus (EBV) is a known determinant for numerous malignancies and may contribute to autoimmune diseases. The underlining mechanisms behind EBV pathologies is not completely understood. Recently, extracellular vesicles (EVs) released from infected cells have been found to produce profound effects on cellular microenvironments. Therefore, in this review we sought to critically evaluate the roles of EVs in EBV pathogenesis and assess their potential therapeutic and diagnostic utility.

Recent findings: EBV-altered EVs are capable of activating signaling cascades and phenotypic changes in recipient cells through the transfer of viral proteins and RNAs. Moreover, several EV-associated microRNAs have encouraging prognostic or diagnostic potential in EBV-associated cancers.

Summary: Current evidence suggests that EBV-modified EVs affect viral pathogenesis and cancer progression. However, further research is needed to investigate the direct role of both viral and host products on recipient cells and the mechanisms driving viral protein and RNA EV packaging and content modification.

Purpose: While most adults are infected Epstein-Barr virus (EBV), 3-5% remain uninfected. The human leukocyte antigen (HLA) complex, which controls many pathogens, may influence infection and disease associated with EBV.

Recent findings: Numerous EBV proteins and miRNAs down-regulate HLA class I and II expression on the cell surface. HLA class II functions as a receptor for EBV entry into B cells. Specific HLA class II alleles correlate with the susceptibility of B cells to EBV infection in vitro and with EBV seropositivity or seronegativity of humans. HLA class I polymorphisms correlate with development and severity of EBV infectious mononucleosis and with the risk of several virus-associated malignancies including nasopharyngeal carcinoma, Hodgkin lymphoma, and post-transplant lymphoproliferative disease.

Significance: These findings indicate that while EBV has evolved to use MHC class II as a receptor for virus entry, polymorphisms in MHC class II and class I influence virus infection and disease.