Alphaviruses are small, enveloped viruses, ~70 nm in diameter, containing a single-stranded, positive-sense, RNA genome. Viruses belonging to this genus are predominantly arthropod-borne viruses, known to cause disease in humans. Their potential threat to human health was most recently exemplified by the 2005 Chikungunya virus outbreak in La Reunion, highlighting the necessity to understand events in the life-cycle of these medically important human pathogens. The replication and propagation of viruses is dependent on entry into permissive cells. Viral entry is initiated by attachment of virions to cells, leading to internalization, and uncoating to release genetic material for replication and propagation. Studies on alphaviruses have revealed entry via a receptor-mediated, endocytic pathway. In this paper, the different stages of alphavirus entry are examined, with examples from Semliki Forest virus, Sindbis virus, Chikungunya virus, and Venezuelan equine encephalitis virus described.

Jason Yat-Sing Leung

Mary Mah-Lee Ng

Justin Jang Hann Chu

Replication of Alphaviruses: A Review on the Entry Process of Alphaviruses into Cells

Xenotropic murine leukaemia virus-related virus (XMRV) is a recently described retrovirus which has been claimed to infect humans and cause associated pathology. Initially identified in the US in patients with prostate cancer and subsequently in patients with chronic fatigue syndrome, doubt now exists that XMRV is a human pathogen. We studied the prevalence of genetic sequences of XMRV and related MuLV sequences in human prostate cancer, from B cell lymphoma patients and from UK blood donors. Nucleic acid was extracted from fresh prostate tissue biopsies, formalin-fixed paraffin-embedded (FFPE) prostate tissue and FFPE B-cell lymphoma. The presence of XMRV-specific LTR or MuLV generic gag-like sequences was investigated by nested PCR. To control for mouse DNA contamination, a PCR that detected intracisternal A-type particle (IAP) sequences was included. In addition, DNA and RNA were extracted from whole blood taken from UK blood donors and screened for XMRV sequences by real-time PCR. XMRV or MuLV-like sequences were not amplified from tissue samples. Occasionally MuLV gag and XMRV-LTR sequences were amplified from Indian prostate cancer samples, but were always detected in conjunction with contaminating murine genomic DNA. We found no evidence of XMRV or MuLV infection in the UK blood donors.

Mark James Robinson

Philip William Tuke

Otto Erlwein

Kate I. Tettmar

Steve Kaye

Kikkeri N. Naresh

Anup Patel

Marjorie M. Walker

Takahiro Kimura

Ganesh Gopalakrishnan

Richard S. Tedder

Myra O. McClure

No Evidence of XMRV or MuLV Sequences in Prostate Cancer, Diffuse Large B-Cell Lymphoma, or the UK Blood Donor Population

Few natural intergenotypic hepatitis C virus (HCV) recombinants have been characterised, and only RF1&#x5f;2k/1b has demonstrated widespread transmission. The near-full length genome sequences for two cases of 2k/1b recombinants (CYHCV037 and CYHCV093) sampled in Cyprus were obtained using strain-specific RT-PCR amplification and sequencing protocols. Sequence analysis confirmed their similarity with the original RF1&#x5f;2k/1b strain from St. Petersburg, N687. These two isolates significantly contribute to the sequence data available on this recombinant and confirm its increasing spread among individuals from Eastern Europe, and its association with transmission through intravenous drug use. Phylogenetic analyses reveal clustering of the sequence 3&#x2032; to the recombination point, not seen in the topology of the 5&#x2032; sequences, implying a more complicated evolutionary history than that held to date. The increasing cases of HCV recombinant strains underline the requirement of their contribution to the standardised rules of HCV classification and nomenclature, molecular epidemiology, diagnosis, and treatment.

Victoria L. Demetriou

Eftychia Kyriakou

Leondios G. Kostrikis

Near-Full Genome Characterisation of Two Natural Intergenotypic 2k/1b Recombinant Hepatitis C Virus Isolates

Virus entry is a multistep process that triggers various cellular pathways that interconnect into a complex network; yet the molecular complexity of this network remains largely elusive. Here, by employing systems biology approaches, we reveal a systemic virus-entry network initiated by human cytomegalovirus (HCMV), a widespread opportunistic pathogen. This network contains ten functional modules (i.e., groups of proteins) that coordinately respond to HCMV entry. Functional modules activated (up- and downregulated) in this network dramatically decline shortly within 25&#x2009;minutes post infection. While modules annotated as receptor system, ion transport, and immune response are continuously activated during the entire process of HCMV entry, those annotated for cell adhesion and skeletal movement are specifically activated during viral early attachment. The up-regulated network contains various functional modules, such as cell surface receptors, skeletal development, endocytosis, ion transport, and chromatin remodeling.  Interestingly, macromolecule metabolism and chromatin remodeling module predominates this over-expressed system, suggesting that the fundamental nuclear process modulation is one of the most important events in HCMV entry. The entire up-regulated network is primarily controlled by multiple elements like SLC10A1. Thus, virus entry triggers multiple cellular processes especially nuclear processes to facilitate its entry.

Anyou Wang

Li Ren

Hong Li

A Systemic Network Triggered by Human Cytomegalovirus Entry

The life cycle of Kaposi's sarcoma-associated herpesvirus (KSHV) consists of latent and lytic replication phases. During latent infection, only a limited number of KSHV genes are expressed. However, this phase of replication is essential for persistent infection, evasion of host immune response, and induction of KSHV-related malignancies. KSHV reactivation from latency produces a wide range of viral products and infectious virions. The resulting de novo infection and viral lytic products modulate diverse cellular pathways and stromal microenvironment, which promote the development of Kaposi's sarcoma (KS). The mechanisms controlling KSHV latency and reactivation are complex, involving both viral and host factors, and are modulated by diverse environmental factors. Here, we review the cellular and molecular basis of KSHV latency and reactivation with a focus on the most recent advancements in the field.

Fengchun Ye

Xiufen Lei

Shou-Jiang Gao

Mechanisms of Kaposi's Sarcoma-Associated Herpesvirus Latency and Reactivation

In 1999, two independent groups identified plasmacytoid dendritic cells (PDC) as major type I interferon- (IFN-) producing cells in the blood. Since then, evidence is accumulating that PDC are a multifunctional cell population effectively coordinating innate and adaptive immune responses. This paper focuses on the role of different immune cells and their interactions in the surveillance of alpha herpes virus infections, summarizes current knowledge on PDC surface receptors and their role in direct cell-cell contacts, and develops a risk factor model for the clinical implications of herpes simplex and varicella zoster virus reactivation. Data from studies involving knockout mice and cell-depletion experiments as well as human studies converge into a “spider web”, in which the direct and indirect crosstalk between many cell populations tightly controls acute, latent, and recurrent alpha herpes virus infections. Notably, cells involved in innate immune regulations appear to shape adaptive immune responses more extensively than previously thought.

Philipp Schuster

Jan Bernardin Boscheinen

Karin Tennert

Barbara Schmidt

The Role of Plasmacytoid Dendritic Cells in Innate and Adaptive Immune Responses against Alpha Herpes Virus Infections

The resistance of cytomegalovirus (CMV) to ganciclovir or valganciclovir is a factor in therapeutic failure and disease progression. CMV strains resistant to ganciclovir or valganciclovir have been associated with specific mutations in the UL97 and UL54 genes. Sequencing of both CMV UL97 and UL54 genes was performed to detect the presence of CMV antiviral resistance in six patients who received ganciclovir (and/or valganciclovir) and had prolonged detectable CMV DNA in their blood during antiviral treatment. Sequencing results showed no specific mutations in either UL97 or UL54 gene of CMV and therefore the CMV strains in kidney transplant patients who received ganciclovir either prophylactically or therapeutically were from the wild type. Our results suggest that CMV management and immunosuppression protocols for kidney transplant patients followed in the Organ Transplant Centre, Kuwait, is very effective in reducing the opportunity of developing CMV antiviral resistance.

Nada Madi

Widad Al-Nakib

Alexander Pacsa

Does Cytomegalovirus Develop Resistance following Antiviral Prophylaxis and Treatment in Renal Transplant Patients in Kuwait?

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Advances in Virology publishes articles in all aspect of viruses and viral diseases. Topics covered include viral structure, function, and genetics, as well as virus-host interactions, viral disease outbreaks, and antiviral therapeutics.

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Advances in Virology - Table of contents 2011

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Advances in Virology publishes articles in all aspect of viruses and viral diseases. Topics covered include viral structure, function, and genetics, as well as virus-host interactions, viral disease outbreaks, and antiviral therapeutics.

Advances in Virology