Oxygen and viruses: a breathing story.

The effect of oxygen on virus replication is complex, and the role of hypoxia-inducible factor 1α (HIF-1α) in the metabolism of virus-infected cells remains uncertain. Solid tumours are hypoxic, and some viruses use this low oxygen tension level to facilitate their replication in tumour cells, thereby causing cell lysis. In addition, the interactions between viruses and HIF-1α may stimulate a trained immunity. However, the evolutionary basis for the oxygen regulatory mechanism of virus replication is ill-defined and requires further investigation.

Une question de terrain : signification de la persistance de l'ADN du parvovirus B19.

The discovery of the human parvovirus B19 was done by Yvonne Cossart in 1975. In addition to fifth disease and aplastic crisis numerous clinical manifestations have been associated with B19 infections. Routine virological diagnosis is made by the detection of specific IgM and sometimes by the detection of viral DNA. Some clinicians are perplexed by the persistence of B19 DNAemia after acute infections. In this point of view we try to discuss this problematic.

Aging of the brain, dementias, role of infectious proteins: facts and theories.

Neurodegenerative diseases, including Alzheimer's, Parkinson's and prion diseases are a major and growing public health issue for aging populations as aging is the greatest risk factor for neurodegeneration. Protein misfolding and spreading are common to these neurodegenerative diseases. There are many high-quality reviews concerning these diseases; also in this brief chapter, I have tried to give a summary of the principal points involved in the pathogenesis of these three clinical entities.

Oxygen tension level and human viral infections.

The role of oxygen tension level is a well-known phenomenon that has been studied in oncology and radiotherapy since about 60 years. Oxygen tension may inhibit or stimulate propagation of viruses in vitro as well as in vivo. In turn modulating oxygen metabolism may constitute a novel approach to treat viral infections as an adjuvant therapy. The major transcription factor which regulates oxygen tension level is hypoxia-inducible factor-1 alpha (HIF-1α). Down-regulating the expression of HIF-1α is a possible method in the treatment of chronic viral infection such as human immunodeficiency virus infection, chronic hepatitis B and C viral infections and Kaposi sarcoma in addition to classic chemotherapy. The aim of this review is to supply an updating concerning the influence of oxygen tension level in human viral infections and to evoke possible new therapeutic strategies regarding this environmental condition.

Concise review: Anemia caused by viruses.

Most of the viruses known to be associated with anemia in human tend to persistently infect their host and are noncytopathic or poorly cytopathic for blood cell progenitors. Infections with Epstein-Barr virus, cytomegalovirus, varicella-zoster virus, human herpes virus 6 (HHV-6), B19 parvovirus, human immunodeficiency virus, hepatitis A and C viruses and the putative viral agent associated with non-A-G post-hepatitis aplastic anemia have been reported in association with anemia. Nevertheless, a direct cytotoxic effect on erythroid progenitors has been clearly demonstrated only for human parvovirus B19 and evocated for HHV-6. A major role for destructive immunity is strongly suspected in the pathogenesis of anemia associated with the other viral infections. Host genes play a role in the occurrence of virus-induced anemia in animal models, and there are some evidences that genetic background could also influence the occurrence of virus-associated anemia in human.

Advances in human B19 erythrovirus biology.

Since its discovery, human parvovirus B19 (B19V), now termed erythrovirus, has been associated with many clinical situations (neurological and myocardium infections, persistent B19V DNAemia) in addition to the prototype clinical manifestations, i.e., erythema infectiosum and erythroblastopenia crisis. In 2002, the use of new molecular tools led to the characterization of three different genotypes of human B19 erythrovirus. Although the genomic organization is conserved, the geographic distribution of the different genotypes varies worldwide, and the nucleotidic divergences can impact the molecular diagnosis of B19 virus infection. The cell cycle of the virus remains partially unresolved; however, recent studies have shed light on the mechanism of cell entry and the interactions of B19V proteins with apoptosis pathways.

Hypoxia enhances human B19 erythrovirus gene expression in primary erythroid cells.

Human B19 erythrovirus replicates in erythroid progenitors present in bone marrow and fetal tissues where partial oxygen tension is low. Here we show that infected human primary erythroid progenitor cells exposed to hypoxia (1% O2) in vitro increase viral capsid protein synthesis, virus replication, and virus production. Hypoxia-inducible factor-1 (HIF-1), the main transcription factor involved in the cellular response to reduced oxygenation, is shown to bind an HIF binding site (HBS) located in the distal part of the B19 promoter region, but the precise mechanism involved in the oxygen-sensitive upregulation of viral gene expression remains to be elucidated.

Efficacy and safety of lowering immunosuppression to treat CMV infection in renal transplant recipients on valaciclovir prophylaxis: a pilot study.

BACKGROUND: Routine cytomegalovirus (CMV)-pp65 antigenaemia monitoring shows that some patients will develop pp65 antigenaemia during valaciclovir prophylaxis or after cessation of treatment. The aim of this pilot study was to evaluate the safety and efficacy of lowering immunosuppression in kidney transplant recipients who exhibit mildly symptomatic CMV infections while on valaciclovir prophylaxis. METHODS: We selected 12 patients who experienced mildly symptomatic CMV infections defined as a positive CMV-pp65 antigenaemia test associated with either neutropenia, asthenia or arthralgia, but no fever. All of them received prophylaxis with valaciclovir for at least 3 months. Testing for CMV-pp65 antigenaemia was performed weekly for 6 months. RESULTS: The mildly symptomatic infections occurred at a median interval of 69 days after transplantation-during prophylaxis in eight cases and after valaciclovir discontinuation in the other four cases. All of them were effectively managed by lowering immunosuppressive therapy, leading to the disappearance of symptoms and CMV antigenaemia reduction. No immunological complication or recurrence of CMV infection or disease was noted. I.v. ganciclovir never became necessary. CONCLUSION: The mildly symptomatic CMV infections occurring in valaciclovir-treated patients may be managed efficiently and without immunologic complication by lowering immunosuppressive therapy.

Identification of a nonconventional motif necessary for the nuclear import of the human parvovirus B19 major capsid protein (VP2).

Human parvovirus B19 replicates and encapsidates its genome in the nucleus of erythroid progenitors in vivo and in vitro. We wanted to understand the determinants necessary for the nuclear transport of the major coat protein, VP2, which makes up about 96% of the viral capsid proteins. A nonconsensus basic motif, KLGPRKATGRW, necessary for the nuclear localization of VP2 was identified and shown to be able to import reporter proteins into the nucleus. The sequence is conserved among the VP2 C-terminal region of erythroviruses. This newly identified sequence will facilitate the understanding of the replication of these viruses.