Next Issue
Previous Issue

E-Mail Alert

Add your e-mail address to receive forthcoming issues of this journal:

Journal Browser

Journal Browser

Table of Contents

Viruses, Volume 2, Issue 11 (November 2010), Pages 2404-2558

  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Readerexternal link to open them.
View options order results:
result details:
Displaying articles 1-9
Export citation of selected articles as:

Review

Jump to: Other

Open AccessReview Development of ST-246® for Treatment of Poxvirus Infections
Viruses 2010, 2(11), 2409-2435; doi:10.3390/v2112409
Received: 18 September 2010 / Revised: 26 October 2010 / Accepted: 26 October 2010 / Published: 3 November 2010
Cited by 14 | PDF Full-text (422 KB)
Abstract
ST-246 (Tecovirimat) is a small synthetic antiviral compound being developed to treat pathogenic orthopoxvirus infections of humans. The compound was discovered as part of a high throughput screen designed to identify inhibitors of vaccinia virus-induced cytopathic effects. The antiviral activity is specific [...] Read more.
ST-246 (Tecovirimat) is a small synthetic antiviral compound being developed to treat pathogenic orthopoxvirus infections of humans. The compound was discovered as part of a high throughput screen designed to identify inhibitors of vaccinia virus-induced cytopathic effects. The antiviral activity is specific for orthopoxviruses and the compound does not inhibit the replication of other RNA- and DNA-containing viruses or inhibit cell proliferation at concentrations of compound that are antiviral. ST-246 targets vaccinia virus p37, a viral protein required for envelopment and secretion of extracellular forms of virus. The compound is orally bioavailable and protects multiple animal species from lethal orthopoxvirus challenge. Preclinical safety pharmacology studies in mice and non-human primates indicate that ST-246 is readily absorbed by the oral route and well tolerated with the no observable adverse effect level (NOAEL) in mice measured at 2000 mg/kg and the no observable effect level (NOEL) in non-human primates measured at 300 mg/kg. Drug substance and drug product processes have been developed and commercial scale batches have been produced using Good Manufacturing Processes (GMP). Human phase I clinical trials have shown that ST-246 is safe and well tolerated in healthy human volunteers. Based on the results of the clinical evaluation, once a day dosing should provide plasma drug exposure in the range predicted to be antiviral based on data from efficacy studies in animal models of orthopoxvirus disease. These data support the use of ST-246 as a therapeutic to treat pathogenic orthopoxvirus infections of humans. Full article
(This article belongs to the Special Issue Antivirals Against Poxviruses)
Open AccessReview Inhibition of the Type I Interferon Antiviral Response During Arenavirus Infection
Viruses 2010, 2(11), 2443-2480; doi:10.3390/v2112443
Received: 8 October 2010 / Revised: 22 October 2010 / Accepted: 22 October 2010 / Published: 5 November 2010
Cited by 34 | PDF Full-text (267 KB)
Abstract
Arenaviruses merit interest both as tractable experimental model systems to study acute and persistent viral infections, and as clinically-important human pathogens. Several arenaviruses cause hemorrhagic fever (HF) disease in humans. In addition, evidence indicates that the globally-distributed prototypic arenavirus lymphocytic choriomeningitis virus [...] Read more.
Arenaviruses merit interest both as tractable experimental model systems to study acute and persistent viral infections, and as clinically-important human pathogens. Several arenaviruses cause hemorrhagic fever (HF) disease in humans. In addition, evidence indicates that the globally-distributed prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) is a human pathogen of clinical significance in congenital infections, and also poses a great danger to immunosuppressed individuals. Arenavirus persistence and pathogenesis are facilitated by their ability to overcome the host innate immune response. Mammalian hosts have developed both membrane toll-like receptors (TLR) and cytoplasmic pattern recognition receptors (PRRs) that recognize specific pathogen-associated molecular patterns (PAMPs), resulting in activation of the transcription factors IRF3 or IRF7, or both, which together with NF-κB and ATF-2/c-JUN induce production of type I interferon (IFN-I). IFN-I plays a key role in host anti-microbial defense by mediating direct antiviral effects via up-regulation of IFN-I stimulated genes (ISGs), activating dendritic cells (DCs) and natural killer (NK) cells, and promoting the induction of adaptive responses. Accordingly, viruses have developed a plethora of strategies to disrupt the IFN-I mediated antiviral defenses of the host, and the viral gene products responsible for these disruptions are often major virulence determinants.IRF3- and IRF7-dependent induction of host innate immune responses is frequently targeted by viruses. Thus, the arenavirus nucleoprotein (NP) was shown to inhibit the IFN‑I response by interfering with the activation of IRF3. This NP anti-IFN activity, together with alterations in the number and function of DCs observed in mice chronically infected with LCMV, likely play an important role in LCMV persistence in its murine host. In this review we will discuss current knowledge about the cellular and molecular mechanisms by which arenaviruses can subvert the host innate immune response and their implications for understanding HF arenaviral disease as well as arenavirus persistence in their natural hosts. Full article
(This article belongs to the Special Issue Interferon Antiviral Response and Viral Evasion)
Open AccessReview The Future of HCV Therapy: NS4B as an Antiviral Target
Viruses 2010, 2(11), 2481-2492; doi:10.3390/v2112481
Received: 19 August 2010 / Revised: 28 September 2010 / Accepted: 13 October 2010 / Published: 10 November 2010
Cited by 20 | PDF Full-text (166 KB)
Abstract
Chronic hepatitis C virus (HCV) infection is a major worldwide cause of liver disease, including cirrhosis and hepatocellular carcinoma. It is estimated that more than 170 million individuals are infected with HCV, with three to four million new cases each year. The [...] Read more.
Chronic hepatitis C virus (HCV) infection is a major worldwide cause of liver disease, including cirrhosis and hepatocellular carcinoma. It is estimated that more than 170 million individuals are infected with HCV, with three to four million new cases each year. The current standard of care, combination treatment with interferon and ribavirin, eradicates the virus in only about 50% of chronically infected patients. Notably, neither of these drugs directly target HCV. Many new antiviral therapies that specifically target hepatitis C (e.g. NS3 protease or NS5B polymerase inhibitors) are therefore in development, with a significant number having advanced into clinical trials. The nonstructural 4B (NS4B) protein, is among the least characterized of the HCV structural and nonstructural proteins and has been subjected to few pharmacological studies. NS4B is an integral membrane protein with at least four predicted transmembrane (TM) domains. A variety of functions have been postulated for NS4B, such as the ability to induce the membranous web replication platform, RNA binding and NTPase activity. This review summarizes potential targets within the nonstructural protein NS4B, with a focus on novel classes of NS4B inhibitors. Full article
(This article belongs to the Special Issue Antivirals Against Hepatitis C Virus)
Open AccessReview Role of HIV Subtype Diversity in the Development of Resistance to Antiviral Drugs
Viruses 2010, 2(11), 2493-2508; doi:10.3390/v2112493
Received: 8 October 2010 / Revised: 26 October 2010 / Accepted: 28 October 2010 / Published: 11 November 2010
Cited by 20 | PDF Full-text (108 KB)
Abstract
Despite the fact that over 90% of HIV-1 infected people worldwide harbor non‑subtype B variants of HIV-1, knowledge of resistance mutations in non-B HIV-1 and their clinical relevance is limited. Due to historical delays in access to antiretroviral therapy (ART) on a [...] Read more.
Despite the fact that over 90% of HIV-1 infected people worldwide harbor non‑subtype B variants of HIV-1, knowledge of resistance mutations in non-B HIV-1 and their clinical relevance is limited. Due to historical delays in access to antiretroviral therapy (ART) on a worldwide basis, the vast majority of reports on drug resistance deal with subtype B infections in developed countries. However, both enzymatic and virological data support the concept that naturally occurring polymorphisms among different nonB subtypes can affect HIV-1 susceptibility to antiretroviral drugs (ARVs), the magnitude of resistance conferred by major mutations, and the propensity to acquire some resistance mutations. Tools need to be optimized to assure accurate measurements of drug susceptibility of non-B subtypes. Furthermore, there is a need to recognize that each subtype may have a distinct resistance profile and that differences in resistance pathways may also impact on cross-resistance and the selection of second-line regimens. It will be essential to pay attention to newer drug combinations in well designed long-term longitudinal studies involving patients infected by viruses of different subtypes. Full article
Open AccessReview Molecular Basis for Drug Resistance in HIV-1 Protease
Viruses 2010, 2(11), 2509-2535; doi:10.3390/v2112509
Received: 8 October 2010 / Revised: 22 October 2010 / Accepted: 28 October 2010 / Published: 12 November 2010
Cited by 46 | PDF Full-text (946 KB)
Abstract
HIV-1 protease is one of the major antiviral targets in the treatment of patients infected with HIV-1. The nine FDA approved HIV-1 protease inhibitors were developed with extensive use of structure-based drug design, thus the atomic details of how the inhibitors bind [...] Read more.
HIV-1 protease is one of the major antiviral targets in the treatment of patients infected with HIV-1. The nine FDA approved HIV-1 protease inhibitors were developed with extensive use of structure-based drug design, thus the atomic details of how the inhibitors bind are well characterized. From this structural understanding the molecular basis for drug resistance in HIV-1 protease can be elucidated. Selected mutations in response to therapy and diversity between clades in HIV-1 protease have altered the shape of the active site, potentially altered the dynamics and even altered the sequence of the cleavage sites in the Gag polyprotein. All of these interdependent changes act in synergy to confer drug resistance while simultaneously maintaining the fitness of the virus. New strategies, such as incorporation of the substrate envelope constraint to design robust inhibitors that incorporate details of HIV-1 protease’s function and decrease the probability of drug resistance, are necessary to continue to effectively target this key protein in HIV-1 life cycle. Full article
(This article belongs to the Special Issue HIV Drug Resistance 2010)
Open AccessReview Buying Time—The Immune System Determinants of the Incubation Period to Respiratory Viruses
Viruses 2010, 2(11), 2541-2558; doi:10.3390/v2112541
Received: 22 October 2010 / Revised: 1 November 2010 / Accepted: 2 November 2010 / Published: 18 November 2010
PDF Full-text (1320 KB)
Abstract
Respiratory viruses cause disease in humans characterized by an abrupt onset of symptoms. Studies in humans and animal models have shown that symptoms are not immediate and appear days or even weeks after infection. Since the initial symptoms are a manifestation of [...] Read more.
Respiratory viruses cause disease in humans characterized by an abrupt onset of symptoms. Studies in humans and animal models have shown that symptoms are not immediate and appear days or even weeks after infection. Since the initial symptoms are a manifestation of virus recognition by elements of the innate immune response, early virus replication must go largely undetected. The interval between infection and the emergence of symptoms is called the incubation period and is widely used as a clinical score. While incubation periods have been described for many virus infections the underlying mechanism for this asymptomatic phase has not been comprehensively documented. Here we review studies of the interaction between human pathogenic respiratory RNA viruses and the host with a particular emphasis on the mechanisms used by viruses to inhibit immunity. We discuss the concept of the “stealth phase”, defined as the time between infection and the earliest detectable inflammatory response. We propose that the “stealth phase” phenomenon is primarily responsible for the suppression of symptoms during the incubation period and results from viral antagonism that inhibits major pathways of the innate immune system allowing an extended time of unhindered virus replication. Full article
(This article belongs to the Special Issue Interferon Antiviral Response and Viral Evasion)

Other

Jump to: Review

Open AccessCommentary Detecting Retroviral Sequences in Chronic Fatigue Syndrome
Viruses 2010, 2(11), 2404-2408; doi:10.3390/v2112404
Received: 26 October 2010 / Revised: 2 November 2010 / Accepted: 2 November 2010 / Published: 3 November 2010
Cited by 4 | PDF Full-text (32 KB)
Abstract
XMRV or xenotropic murine leukemia virus-related retrovirus, a recently discovered retrovirus, has been linked to both prostate cancer and chronic fatigue syndrome (CFS). Recently, the teams of Drs. Shyh-Ching Lo and Harvey Alter discovered the presence of sequences closely related to XMRV [...] Read more.
XMRV or xenotropic murine leukemia virus-related retrovirus, a recently discovered retrovirus, has been linked to both prostate cancer and chronic fatigue syndrome (CFS). Recently, the teams of Drs. Shyh-Ching Lo and Harvey Alter discovered the presence of sequences closely related to XMRV in the blood of 86.5% of patients with CFS [1]. These findings are important because since the initial discovery of XMRV in CFS, several studies have failed to find XMRV in specimens collected from CFS patients. While the current study also did not find XMRV in CFS, Lo et al. did detect sequences that belong to polytropic mouse endogenous retroviruses (PMV), which share considerable similarity with XMRV. Criteria for future studies that will help bring greater clarity to the issue of retroviral sequences in CFS are proposed below. Full article
(This article belongs to the Section Editorial)
Open AccessCommentary Making of Viral Replication Organelles by Remodeling Interior Membranes
Viruses 2010, 2(11), 2436-2442; doi:10.3390/v2112436
Received: 8 October 2010 / Revised: 29 October 2010 / Accepted: 1 November 2010 / Published: 5 November 2010
Cited by 11 | PDF Full-text (221 KB)
Abstract
Positive-stranded RNA (+RNA) viruses exploit host cell machinery by subverting host proteins and membranes and altering cellular pathways during infection. To achieve robust replication, some +RNA viruses, such as poliovirus (PV), build special intracellular compartments, called viral replication organelles. A recent work [...] Read more.
Positive-stranded RNA (+RNA) viruses exploit host cell machinery by subverting host proteins and membranes and altering cellular pathways during infection. To achieve robust replication, some +RNA viruses, such as poliovirus (PV), build special intracellular compartments, called viral replication organelles. A recent work from the Altan-Bonnett laboratory [1] gave new insights into the formation of poliovirus replication organelles, which are unique subcellular structures containing many individual replication complexes as a result of dynamic cellular membrane remodeling. Full article
(This article belongs to the Section Editorial)
Open AccessCommentary Mind the Gap: How Some Viruses Infect Their Hosts
Viruses 2010, 2(11), 2536-2540; doi:10.3390/v2112536
Received: 19 October 2010 / Revised: 10 November 2010 / Accepted: 11 November 2010 / Published: 12 November 2010
PDF Full-text (210 KB)
Abstract
Cryo-electron microscopy (Cryo-EM) and cryo-electron tomography (Cryo-ET) provide structural insights into complex biological processes. The podoviridae are dsDNA containing phage with short, non-contractile tails which nevertheless translocate their DNA into the cytoplasm of their host cells. Liu et al. [1] used a [...] Read more.
Cryo-electron microscopy (Cryo-EM) and cryo-electron tomography (Cryo-ET) provide structural insights into complex biological processes. The podoviridae are dsDNA containing phage with short, non-contractile tails which nevertheless translocate their DNA into the cytoplasm of their host cells. Liu et al. [1] used a combination of cryo-EM and cryo-ET to study the structural changes accompanying infection of P. marinus by the phage P-SSP7 and thereby provide unique molecular insight into the process by which the DNA transits from phage to host during infection. Full article
(This article belongs to the Section Editorial)

Journal Contact

MDPI AG
Viruses Editorial Office
St. Alban-Anlage 66, 4052 Basel, Switzerland
viruses@mdpi.com
Tel. +41 61 683 77 34
Fax: +41 61 302 89 18
Editorial Board
Contact Details Submit to Viruses
Back to Top