Selective inhibitory effects of (S)-9-(3-hydroxy-2-phosphonyl-methoxypropyl)adenine and 1-(2'-deoxy-

From a selection of 25 antiviral compounds with specific anti-herpes activity or broad-spectrum antiviral properties, two compounds, namely (S)-9-(3-hydroxy-2-phosphonyl-methoxypropyl)adenine and 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-iodouracil, appeared particularly effective in inhibiting the cytopathogenicity of seal herpesvirus (phocid herpesvirus 1)

Bioinformatics in New Generation Flavivirus Vaccines

Flavivirus infections are the most prevalent arthropod-borne infections world wide, often causing severe disease especially among children, the elderly, and the immunocompromised. In the absence of effective antiviral treatment, prevention through vaccination would greatly reduce morbidity and mortality associated with flavivirus infections. Despite the success of the empirically developed vaccines against yellow fever virus, Japanese encephalitis virus and tick-borne encephalitis virus, there is an increasing need for a more rational design and development of safe and effective vaccines. Several bioinformatic tools are available to support such rational vaccine design. In doing so, several parameters have to be taken into account, such as safety for the target population, overall immunogenicity of the candidate vaccine, and efficacy and longevity of the immune responses triggered. Examples of how bio-informatics is applied to assist in the rational design and improvements of vaccines, particularly flavivirus vaccines, are presented and discussed

The Application of Genomics to Emerging Zoonotic Viral Diseases

Interspecies transmission of pathogens may result in the emergence of new infectious diseases in humans as well as in domestic and wild animals. Genomics tools such as high-throughput sequencing, mRNA expression profiling, and microarray-based analysis of single nucleotide polymorphisms are providing unprecedented ways to analyze the diversity of the genomes of emerging pathogens as well as the molecular basis of the host response to them. By comparing and contrasting the outcomes of an emerging infection with those of closely related pathogens in different but related host species, we can further delineate the various host pathways determining the outcome of zoonotic transmission and adaptation to the newly invaded species. The ultimate challenge is to link pathogen and host genomics data with biological outcomes of zoonotic transmission and to translate the integrated data into novel intervention strategies that eventually will allow the effective control of newly emerging infectious diseases

Development of a quantitative real-time detection assay for hepatitis B virus DNA and comparison with two commercial assays

A highly reproducible and sensitive real-time detection assay based on TaqMan technology was developed for the detection of hepatitis B viru

In vitro replication capacity of HIV-2 variants from long-term aviremic individuals

AbstractTo establish whether efficient suppression of virus replication in HIV-2-infected individuals is associated with low replicative capacity of HIV-2, replication kinetics of HIV-2 variants from long-term aviremic individuals was analyzed and compared with that of the relatively slow-replicating HIV-1 variants from asymptomatics and long-term nonprogressors (AS/LTNP). On average, HIV-2 from aviremic individuals had lower replication rates than HIV-1 variants from AS/LTNP in cells of 8 donors (0.45 log10 [range 0.14–0.77] vs. 0.58 log10 [range 0.32–0.99] pg RT/ml/day, P = 0.036). The relatively low replication rate of HIV-2 compared to HIV-1 variants was not related to different sensitivities to inhibition by CD8+ T cells or different degrees of infectivity. HIV-2 replication rates increased with progressive infection and with switch from CCR5 to CXCR4 usage.The relatively low replicative capacity of HIV-2 variants from aviremic individuals likely contributes to the low viral load and benign course of infection in these individuals

Identification of a new variant in the YMDD motif of the hepatitis B virus polymerase gene selected during lamivudine therapy

A new hepatitis B virus variant selected during lamivudine treatment was detected, in which the methionine (rtM204) in the so-called YMDD motif in the C

MVA-based H5N1 vaccine affords cross-clade protection in mice against influenza A/H5N1 viruses at low doses and after single immunization.

Human infections with highly pathogenic avian influenza viruses of the H5N1 subtype, frequently reported since 2003, result in high morbidity and mortality. It is feared that these viruses become pandemic, therefore the development of safe and effective vaccines is desirable. MVA-based H5N1 vaccines already proved to be effective when two immunizations with high doses were used. Dose-sparing strategies would increase the number of people that can be vaccinated when the amount of vaccine preparations that can be produced is limited. Furthermore, protective immunity is induced ideally after a single immunization. Therefore the minimal requirements for induction of protective immunity with a MVA-based H5N1 vaccine were assessed in mice. To this end, mice were vaccinated once or twice with descending doses of a recombinant MVA expressing the HA gene of influenza virus A/Vietnam/1194/04. The protective efficacy was determined after challenge infection with the homologous clade 1 virus and a heterologous virus derived from clade 2.1, A/Indonesia/5/05 by assessing weight loss, virus replication and histopathological changes. It was concluded that MVA-based vaccines allowed significant dose-sparing and afford cross-clade protection, also after a single immunization, which are favorable properties for an H5N1 vaccine candidate

Dolphin morbillivirus infection in different parts of the Mediterranean Sea

Morbillivirus were isolated from Mediterranean striped dolphins (Stenella coeruleoalba) dying along the coasts of Italy and Greece in 1991. They were antigenically identical to the morbilliviruses isolated from striped dolphins in Spain in 1990

Linking Influenza Virus Tissue Tropism to Population-Level Reproductive Fitness

Influenza virus tissue tropism defines the host cells and tissues that support viral replication and contributes to determining which regions of the respiratory tract are infected in humans. The location of influenza virus infection along the respiratory tract is a key determinant of virus pathogenicity and transmissibility, which are at the basis of influenza burdens in the human population. As the pathogenicity and transmissibility of influenza virus ultimately determine its reproductive fitness at the population level, strong selective pressures will shape influenza virus tissue tropisms that maximize fitness. At present, the relationships between influenza virus tissue tropism within hosts and reproductive fitness at the population level are poorly understood. The selective pressures and constraints that shape tissue tropism and thereby influence the location of influenza virus infection along the respiratory tract are not well characterized. We use mathematical models that link within-host infection dynamics in a spatially-structured human respiratory tract to between-host transmission dynamics, with the aim of characterizing the possible selective pressures on influenza virus tissue tropism. The results indicate that spatial heterogeneities in virus clearance, virus pathogenicity or both, resulting from the unique structure of the respiratory tract, may drive optimal receptor binding affinity-that maximizes influenza virus reproductive fitness at the population level-towards sialic acids with α2,6 linkage to galactose. The expanding cell pool deeper down the respiratory tract, in association with lower clearance rates, may result in optimal infectivity rates-that likewise maximize influenza virus reproductive fitness at the population level-to exhibit a decreasing trend towards deeper regions of the respiratory tract. Lastly, pre-existing immunity may drive influenza virus tissue tropism towards upper regions of the respiratory tract. The propo