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Viruses, Volume 3, Issue 12 (December 2011) – 6 articles , Pages 2374-2477

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845 KiB

Open AccessReview

The Actin Cytoskeleton as a Barrier to Virus Infection of Polarized Epithelial Cells

by Elizabeth Delorme-Axford and Carolyn B. Coyne

Viruses 2011, 3(12), 2462-2477; https://doi.org/10.3390/v3122462 - 21 Dec 2011

Cited by 51 | Viewed by 11950

Abstract

Many diverse viruses target a polarized epithelial monolayer during host invasion. The polarized epithelium is adept at restricting the movement of solutes, ions, macromolecules, and pathogens across the mucosa. This regulation can be attributed to the presence of a junctional complex between adjacent cells and to an intricate network of actin filaments that provides support to the subapical membrane and stabilizes intercellular junctions. It is therefore not surprising that many viruses have evolved highly varied strategies to dissolve or modulate the cortical actin meshwork to promote infection of polarized cells. In this review, we will discuss the cell biological properties of the actin cytoskeleton in polarized epithelial cells and review the known mechanisms utilized by viral pathogens to manipulate this system in order to facilitate their infection. Full article

(This article belongs to the Special Issue Cytoskeleton in Viral Infections)

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Open AccessCommunication

The Human Lung Adenocarcinoma Cell Line EKVX Produces an Infectious Xenotropic Murine Leukemia Virus

by Joan L. Cmarik, Jami A. Troxler, Charlotte A. Hanson, Xiang Zhang and Sandra K. Ruscetti

Viruses 2011, 3(12), 2442-2461; https://doi.org/10.3390/v3122442 - 19 Dec 2011

Cited by 5 | Viewed by 10138

Abstract

The cell lines of the NCI-60 panel represent different cancer types and have been widely utilized for drug screening and molecular target identification. Screening these cell lines for envelope proteins or gene sequences related to xenotropic murine leukemia viruses (X-MLVs) revealed that one cell line, EKVX, was a candidate for production of an infectious gammaretrovirus. The presence of a retrovirus infectious to human cells was confirmed by the cell-free transmission of infection to the human prostate cancer cell line LNCaP. Amplification and sequencing of additional proviral sequences from EKVX confirmed a high degree of similarity to X-MLV. The cell line EKVX was established following passage of the original tumor cells through nude mice, providing a possible source of the X-MLV found in the EKVX cells. Full article

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2192 KiB

Open AccessArticle

Dynamics of Persistent and Acute Deformed Wing Virus Infections in Honey Bees, Apis mellifera

by Gennaro Di Prisco, Xuan Zhang, Francesco Pennacchio, Emilio Caprio, Jilian Li, Jay D. Evans, Gloria DeGrandi-Hoffman, Michele Hamilton and Yan Ping Chen

Viruses 2011, 3(12), 2425-2441; https://doi.org/10.3390/v3122425 - 14 Dec 2011

Cited by 74 | Viewed by 12851

Abstract

The dynamics of viruses are critical to our understanding of disease pathogenesis. Using honey bee Deformed wing virus (DWV) as a model, we conducted field and laboratory studies to investigate the roles of abiotic and biotic stress factors as well as host health conditions in dynamics of virus replication in honey bees. The results showed that temperature decline could lead to not only significant decrease in the rate for pupae to emerge as adult bees, but also an increased severity of the virus infection in emerged bees, partly explaining the high levels of winter losses of managed honey bees, Apis mellifera, around the world. By experimentally exposing adult bees with variable levels of parasitic mite Varroa destructor, we showed that the severity of DWV infection was positively correlated with the density and time period of Varroa mite infestation, confirming the role of Varroa mites in virus transmission and activation in honey bees. Further, we showed that host conditions have a significant impact on the outcome of DWV infection as bees that originate from strong colonies resist DWV infection and replication significantly better than bee originating from weak colonies. The information obtained from this study has important implications for enhancing our understanding of host‑pathogen interactions and can be used to develop effective disease control strategies for honey bees. Full article

(This article belongs to the Special Issue Insect Viruses)

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Open AccessReview

The Use of Fluorescence Microscopy to Study the Association Between Herpesviruses and Intrinsic Resistance Factors

by Roger D. Everett

Viruses 2011, 3(12), 2412-2424; https://doi.org/10.3390/v3122412 - 7 Dec 2011

Cited by 7 | Viewed by 6987

Abstract

Intrinsic antiviral resistance is a branch of antiviral defence that involves constitutively expressed cellular proteins that act within individual infected cells. In recent years it has been discovered that components of cellular nuclear structures known as ND10 or PML nuclear bodies contribute to intrinsic resistance against a variety of viruses, notably of the herpesvirus family. Several ND10 components are rapidly recruited to sites that are closely associated with herpes simplex virus type 1 (HSV-1) genomes during the earliest stages of infection, and this property correlates with the efficiency of ND10 mediated restriction of HSV-1 replication. Similar but distinct recruitment of certain DNA damage response proteins also occurs during infection. These recruitment events are inhibited in a normal wild type HSV-1 infection by the viral regulatory protein ICP0. HSV‑1 mutants that do not express ICP0 are highly susceptible to repression through intrinsic resistance factors, but they replicate more efficiently in cells depleted of certain ND10 proteins or in which ND10 component recruitment is inefficient. This article presents the background to this recruitment phenomenon and summaries how it is conveniently studied by fluorescence microscopy. Full article

(This article belongs to the Special Issue Frontiers in Imaging)

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Open AccessArticle

High Throughput Method to Quantify Anterior-Posterior Polarity of T-Cells and Epithelial Cells

by Charletha V. Irvin-Wilson, Justin Y. Newberg, Kathleen Kong, Ronald T. Javier and Susan J. Marriott

Viruses 2011, 3(12), 2396-2411; https://doi.org/10.3390/v3122396 - 28 Nov 2011

Viewed by 6858

Abstract

The virologic synapse (VS), which is formed between a virus-infected and uninfected cell, plays a central role in the transmission of certain viruses, such as HIV and HTLV-1. During VS formation, HTLV-1-infected T-cells polarize cellular and viral proteins toward the uninfected T-cell. This polarization resembles anterior-posterior cell polarity induced by immunological synapse (IS) formation, which is more extensively characterized than VS formation and occurs when a T-cell interacts with an antigen-presenting cell. One measure of cell polarity induced by both IS or VS formation is the repositioning of the microtubule organizing center (MTOC) relative to the contact point with the interacting cell. Here we describe an automated, high throughput system to score repositioning of the MTOC and thereby cell polarity establishment. The method rapidly and accurately calculates the angle between the MTOC and the IS for thousands of cells. We also show that the system can be adapted to score anterior-posterior polarity establishment of epithelial cells. This general approach represents a significant advancement over manual cell polarity scoring, which is subject to experimenter bias and requires more time and effort to evaluate large numbers of cells. Full article

(This article belongs to the Special Issue Frontiers in Imaging)

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Open AccessReview

The Human Antibody Response to Dengue Virus Infection

by Wahala M. P. B. Wahala and Aravinda M. De Silva

Viruses 2011, 3(12), 2374-2395; https://doi.org/10.3390/v3122374 - 25 Nov 2011

Cited by 265 | Viewed by 25242

Abstract

Dengue viruses (DENV) are the causative agents of dengue fever (DF) and dengue hemorrhagic fever (DHF). Here we review the current state of knowledge about the human antibody response to dengue and identify important knowledge gaps. A large body of work has demonstrated that antibodies can neutralize or enhance DENV infection. Investigators have mainly used mouse monoclonal antibodies (MAbs) to study interactions between DENV and antibodies. These studies indicate that antibody neutralization of DENVs is a “multi-hit” phenomenon that requires the binding of multiple antibodies to neutralize a virion. The most potently neutralizing mouse MAbs bind to surface exposed epitopes on domain III of the dengue envelope (E) protein. One challenge facing the dengue field now is to extend these studies with mouse MAbs to better understand the human antibody response. The human antibody response is complex as it involves a polyclonal response to primary and secondary infections with 4 different DENV serotypes. Here we review studies conducted with immune sera and MAbs isolated from people exposed to dengue infections. Most dengue-specific antibodies in human immune sera are weakly neutralizing and bind to multiple DENV serotypes. The human antibodies that potently and type specifically neutralize DENV represent a small fraction of the total DENV-specific antibody response. Moreover, these neutralizing antibodies appear to bind to novel epitopes including complex, quaternary epitopes that are only preserved on the intact virion. These studies establish that human and mouse antibodies recognize distinct epitopes on the dengue virion. The leading theory proposed to explain the increased risk of severe disease in secondary cases is antibody dependent enhancement (ADE), which postulates that weakly neutralizing antibodies from the first infection bind to the second serotype and enhance infection of FcγR bearing myeloid cells such as monocytes and macrophages. Here we review results from human, animal and cell culture studies relevant to the ADE hypothesis. By understanding how human antibodies neutralize or enhance DENV, it will be possible to better evaluate existing vaccines and develop the next generation of novel vaccines. Full article

(This article belongs to the Special Issue Recent Progress in Dengue Virus Research)

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