Complexity Of Virus-host Interactions Research Articles

Bacterial RecA Protein Promotes Adenoviral Recombination during In Vitro Infection.

Adenovirus infections in humans are common and sometimes lethal. Adenovirus-derived vectors are also commonly chosen for gene therapy in human clinical trials. We have shown in previous work that homologous recombination between adenoviral genomes of human adenovirus species D (HAdV-D), the largest and fastest growing HAdV species, is responsible for the rapid evolution of this species. Because adenovirus infection initiates in mucosal epithelia, particularly at the gastrointestinal, respiratory, genitourinary, and ocular surfaces, we sought to determine a possible role for mucosal microbiota in adenovirus genome diversity. By analysis of known recombination hot spots across 38 human adenovirus genomes in species D (HAdV-D), we identified nucleotide sequence motifs similar to bacterial Chi sequences, which facilitate homologous recombination in the presence of bacterial Rec enzymes. These motifs, referred to here as ChiAD, were identified immediately 5' to the sequence encoding penton base hypervariable loop 2, which expresses the arginine-glycine-aspartate moiety critical to adenoviral cellular entry. Coinfection with two HAdV-Ds in the presence of an Escherichiacoli lysate increased recombination; this was blocked in a RecA mutant strain, E.coli DH5α, or upon RecA depletion. Recombination increased in the presence of E.coli lysate despite a general reduction in viral replication. RecA colocalized with viral DNA in HAdV-D-infected cell nuclei and was shown to bind specifically to ChiAD sequences. These results indicate that adenoviruses may repurpose bacterial recombination machinery, a sharing of evolutionary mechanisms across a diverse microbiota, and unique example of viral commensalism.IMPORTANCE Adenoviruses are common human mucosal pathogens of the gastrointestinal, respiratory, and genitourinary tracts and ocular surface. Here, we report finding Chi-like sequences in adenovirus recombination hot spots. Adenovirus coinfection in the presence of bacterial RecA protein facilitated homologous recombination between viruses. Genetic recombination led to evolution of an important external feature on the adenoviral capsid, namely, the penton base protein hypervariable loop 2, which contains the arginine-glycine-aspartic acid motif critical to viral internalization. We speculate that free Rec proteins present in gastrointestinal secretions upon bacterial cell death facilitate the evolution of human adenoviruses through homologous recombination, an example of viral commensalism and the complexity of virus-host interactions, including regional microbiota.

Global Profiling of the Cellular Alternative RNA Splicing Landscape during Virus-Host Interactions

Alternative splicing (AS) is a central mechanism of genetic regulation which modifies the sequence of RNA transcripts in higher eukaryotes. AS has been shown to increase both the variability and diversity of the cellular proteome by changing the composition of resulting proteins through differential choice of exons to be included in mature mRNAs. In the present study, alterations to the global RNA splicing landscape of cellular genes upon viral infection were investigated using mammalian reovirus as a model. Our study provides the first comprehensive portrait of global changes in the RNA splicing signatures that occur in eukaryotic cells following infection with a human virus. We identify 240 modified alternative splicing events upon infection which belong to transcripts frequently involved in the regulation of gene expression and RNA metabolism. Using mass spectrometry, we also confirm modifications to transcript-specific peptides resulting from AS in virus-infected cells. These findings provide additional insights into the complexity of virus-host interactions as these splice variants expand proteome diversity and function during viral infection.

The Surprising Complexity of Virus-Host Cell Interaction Revealed by the Powerful Systems Biology Approaches of Genomics and Proteomics

Understanding interaction between viruses and host cells during infection process is the first step in discovering appropriate drugs and vaccines against viral diseases. Advance technologies based on genomics and proteomics approaches provide great tools to disclose the complexity of virus-host interaction. In this essay, the application of RNAi screens method and proteomics-based approaches on influenza virus will be elucidated as an example. Using those methods, the primary factors controlling viral replication pathway were discovered. These findings are useful for the development of potential strategies to overcome viral diseases.

Herpes Simplex Varicella and Zoster: Clinical Manifestations and Treatment.

Few viruses display the multiple clinical manifestations or the complexity of virus-host interaction as the herpesviruses. The manifestations of infections with herpes simplex virus may range from encephalitis to inapparent illness. The virus may remain latent for years and recurrent lesions develop for yet undefined reasons. Antibodies develop against the virus but reinfection is possible. More recently, it has become apparent that patients whose immune mechanisms are compromised by certain types of malignancies, malnutrition, or drug therapy are susceptible to severe life-threatening infections by members of the herpesvirus group. Finally, several herpesviruses may be etiologically related to human malignancies. For these reasons, there is considerable interest among practitioners and researchers in the herpesviruses. The human herpesviruses include herpes simplex viruses type 1 and type 2, varicella-zoster virus, cytomegalovirus and EB virus. The authors of the book have confined their topics to the herpes simplex viruses, varicella-zoster virus, and to a