Dynamics of viral RNA synthesis during measles virus infection

We propose a reference model of the kinetics of a viral RNA-dependent RNA polymerase (vRdRp) activities and its regulation during infection of eucaryotic cells. After measles virus infects a cell, mRNAs from all genes immediately start to accumulate linearly over the first 5 to 6 h and then exponentially until approximately 24 h. The change from a linear to an exponential accumulation correlates with de novo synthesis of vRdRp from the incoming template. Expression of the virus nucleoprotein (N) prior to infection shifts the balance in favor of replication. Conversely, inhibition of protein synthesis by cycloheximide favors the latter. The in vivo elongation speed of the viral polymerase is approximately 3 nucleotides/s. A similar profile with fivefold-slower kinetics can be obtained using a recombinant virus expressing a structurally altered polymerase. Finally, virions contain only encapsidated genomic, antigenomic, and 5'-end abortive replication fragment RNAs.     

Dynamics of nutrient-phytoplankton interaction in the presence of viral infection

The present paper deals with the problem of a nutrient-phytoplankton (N-P) populations where phytoplankton population is divided into two groups, namely susceptible phytoplankton and infected phytoplankton. Conditions for coexistence or extinction of populations are derived taking into account general nutrient uptake functions and Holling type-II functional response as an example. It is observed that the three component systems persist when the infected phytoplankton population is not able to consume nutrient.     

Dynamics of viral evolution and CTL responses in HIV-1 infection

Improved understanding of the dynamics of host immune responses and viral evolution is critical for effective HIV-1 vaccine design. We comprehensively analyzed Cytotoxic T-lymphocyte (CTL)-viral epitope dynamics in an antiretroviral therapy-naïve subject over the first four years of HIV-1 infection. We found that CTL responses developed sequentially and required constant antigenic stimulation for maintenance. CTL responses exerting strong selective pressure emerged early and led to rapid escape, proliferated rapidly and were predominant during acute/early infection. Although CTL responses to a few persistent epitopes developed over the first two months of infection, they proliferated slowly. As CTL epitopes were replaced by mutational variants, the corresponding responses immediately declined, most rapidly in the cases of strongly selected epitopes. CTL recognition of epitope variants, via cross-reactivity and de novo responses, was common throughout the period of study. Our data demonstrate that HIV-specific CTL responses, especially in the critical acute/early stage, were focused on regions that are prone to escape. Failure of CTL responses to strongly target functional or structurally critical regions of the virus, as well as the sequential cascade of CTL responses, followed closely by viral escape and decline of the corresponding responses, likely contribute to a lack of sustainable viral suppression. Focusing early and rapidly proliferating CTL on persistent epitopes may be essential for durable viral control in HIV-1 infection.     

microRNA与病毒感染

microRNA是一类新近发现的由20-23个核苷酸构成的非编码RNA分子,它在生命进程中起着重要作用.病毒的复制和繁殖依赖于宿主细胞,而且对细胞环境的变化敏感.研究表明宿主和病毒都可以编码microRNA,病毒可通过小RNA介导的干扰作用影响宿主细胞,也能利用自身的"独特战略"改变宿主细胞从而满足自己生存的需求,所以,宿主与病毒间存在microRNA-mRNA相互作用的机制.尽管时microRNA与病毒感染的关系研究时间不长,但目前的研究结果为我们理解病毒和宿主之间的相互作用提供了一条途径,并为寻找病毒感染的生物标志物和治疗方法提供了新的思路.     

微囊泡与病毒感染

微囊泡(microvesicle)是细胞释放到胞外的膜性囊泡,其能将所含的蛋白质、脂类和核酸分子转运给其他细胞,从而介导细胞间通讯。作为严格细胞内寄生的微生物,病毒能利用微囊泡的生物合成和扩散途径进行病毒粒子的组装、出芽和传递,同时将病毒蛋白或基因组包装入微囊泡中。这些病毒修饰的囊泡能介导病毒在机体内的感染和扩散,或导致免疫细胞损伤以及耐受抗体的中和,从而逃避宿主免疫应答,引起持续性感染。重要的是,微囊泡介导的病毒感染打破了对病毒在体内扩散和感染时必须有病毒粒子存在的传统认知。对微囊泡与病毒感染进行综述,以促进对微囊泡介导病毒感染和抑制宿主免疫应答分子机制的了解。     

Microvesicles and viral infection

Cells secrete various membrane-enclosed microvesicles from their cell surface (shedding microvesicles) and from internal, endosome-derived membranes (exosomes). Intriguingly, these vesicles have many characteristics in common with enveloped viruses, including biophysical properties, biogenesis, and uptake by cells. Recent discoveries describing the microvesicle-mediated intercellular transfer of functional cellular proteins, RNAs, and mRNAs have revealed additional similarities between viruses and cellular microvesicles. Apparent differences include the complexity of viral entry, temporally regulated viral expression, and self-replication proceeding to infection of new cells. Interestingly, many virally infected cells secrete microvesicles that differ in content from their virion counterparts but may contain various viral proteins and RNAs. For the most part, these particles have not been analyzed for their content or functions during viral infection. However, early studies of microvesicles (L-particles) secreted from herpes simplex virus-infected cells provided the first evidence of microvesicle-mediated intercellular communication. In the case of Epstein-Barr virus, recent evidence suggests that this tumorigenic herpesvirus also utilizes exosomes as a mechanism of cell-to-cell communication through the transfer of signaling competent proteins and functional microRNAs to uninfected cells. This review focuses on aspects of the biology of microvesicles with an emphasis on their potential contributions to viral infection and pathogenesis.     

Dynamics of filamentous viral RNPs prior to egress

The final step in the maturation of paramyxoviruses, orthomyxoviruses and viruses of several other families, entails the budding of the viral nucleocapsid through the plasma membrane of the host cell. Many medically important viruses, such as influenza, parainfluenza, respiratory syncytial virus (RSV) and Ebola, can form filamentous particles when budding. Although filamentous virions have been previously studied, details of how viral filaments bud from the plasma membrane remain largely unknown. Using molecular beacon (MB)-fluorescent probes to image the viral genomic RNA (vRNA) of human RSV (hRSV) in live Vero cells, the dynamics of assembled viral filaments was observed to consist of three primary types of motion prior to egress from the plasma membrane: (i) filament projection and rotation, (ii) migration and (iii) non-directed motion. In addition, from information gained by imaging the 3D distribution of cellular vRNA, observing and characterizing vRNA dynamics, imaging vRNA/Myosin Va colocalization, and studying the effects of cytochalasin D (actin depolymerizing agent) exposure, a model for filamentous virion egress is presented.     

Dynamics of viral hepatitis A morbidity in Minsk

The results of the analysis of hepatitis A morbidity during the period of 1996 - 2001, are presented. The cyclic character of this morbidity in its dynamics over the period of several years was noted with the maximum morbidity level reached in 2000. The monthly dynamics of hepatitis A morbidity reflected its seasonal character with the maximum increase in autumn and winter. The virological control of drinking water revealed its contamination in spring and summer, with no subsequent rise in morbidity. The control of sewage reflected the emergence of the virus in the city collector in accordance with the increased morbidity.     

The nucleolus and viral infection

The nucleolus is a subnuclear structure of eukaryocytes. It was thought that nucleolus only participates in the biogenesis and processing of rRNA. However, more and more evidence shows that it has many other functions, such as tRNA precursor processing, stress sensing and it is also involved in gene silencing, senescence and cell cycle regulation. Here, we summarize the recent understandings about the nucleolar functions, the regulation of nucleolar localization of proteins and the role that the nucleolus plays in virus infection, in which some related studies of Herpes simplex virus type 1 (HSV-1) US11, UL24 and bovine herpesvirus-1 infected cell protein 27 (BICP27) carried out in our lab will also be included.     

TLR family and viral infection

The immune system has been divided into innate and adaptive component, each of which has different roles and functions in defending the organism against foreign agents, such as bacteria and viruses. An important advance in our understanding of early events in microbial recognition and subsequent development of immune responses was the identification of Toll-like receptors (TLRs) as key molecules of the innate immune systems. The family of TLRs in vertebrates detects conserved structures found in a broad range of pathogens and triggers innate immune responses. At present, 11 members of the TLR family have been identified. A subset of TLRs recognize viral components and induce antiviral responses by producing type I interferons. Recent accumulating evidence has clarified signaling pathways triggered by TLRs in viral infection.     

Integrin activation and viral infection

Integrins are members of a ubiquitous membrane receptor family which includes 18 different α subunits and 8 β subunits forming more than 20 α/β heterodimers. Integrins play key functions in vascular endothelial cell and tumour cell adhesion, lymphocyte trafficking, tumor growth and viral infection. Current understanding of the molecular basis of integrins as viral receptors has been achieved through many decades of study into the biology of transmembrane glycoproteins and their interactions with several viruses. This review provides a summary of the current knowledge on the molecular bases of interactions between viruses and integrins, which are of potential practical significance. Inhibition of virus-integrin interactions at the points of virus attachment or entry will provide a novel approach for the therapeutic treatment of viral diseases. Foundation item: The National key Basic Research (973) Program (2005CB523201) and National Key Technology R&D Program (2006BAD06A14)     

Innate barriers to viral infection

Innate immunity represents the foremost barrier to viral infection. In order to infect a cell efficiently, viruses need to evade innate immune effectors such as interferons and inflammatory cytokines. Pattern recognition receptors can detect viral components or pathogen-associated molecular patterns. These receptors then elicit innate immune responses that result in the generation of type I interferons and proinflammatory cytokines. Organized by the Society for General Microbiology, one session of this conference focused on the current state-of-the-art knowledge on innate barriers to infection of different RNA and DNA viruses. Experts working on innate immunity in the context of viral infection provided insight into different aspects of innate immune recognition and also discussed areas for future research. Here, we provide an overview of the session on innate barriers to infection.