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A number of experimental elastic light scattering studies have been performed in the past few years with the aim of developing automated in vivo tools for differentiating a healthy red blood cell from a Plasmodium falciparum infected cell. This paper examines some theoretical aspects of the problem. An attempt has been made to simulate the scattering patterns of healthy as well as infected individual red blood cells. Two models, namely, a homogeneous sphere model and a coated sphere model have been considered. The scattering patterns predicted by these models are examined. A possible method for discriminating infected red blood cells from healthy ones has been suggested.

Host-pathogen arms race is a universal, central aspect of the evolution of life. Most organisms evolved several distinct yet interacting strategies of anti-pathogen defense including resistance to parasite invasion, innate and adaptive immunity, and programmed cell death (PCD). The PCD is the means of last resort, a suicidal response to infection that is activated when resistance and immunity fail. An infected cell faces a decision between active defense and altruistic suicide or dormancy induction, depending on whether immunity is “deemed” capable of preventing parasite reproduction and consequent infection of other cells. In bacteria and archaea, immunity genes typically colocalize with PCD modules, such as toxins-antitoxins, suggestive of immunity-PCD coupling, likely mediated by shared proteins that sense damage and “predict” the outcome of infections. In type VI CRISPR-Cas systems, the same enzyme that inactivates the target RNA might execute cell suicide, in a case of ultimate integration of immunity and PCD.

In microbiology, and in particular in virus research, electron microscopy (EM) is an important tool, offering a broad approach for investigating viral structure throughout their intracellular and extracellular life cycles. Currently, molecular tools and rapid developments in advanced light microscopy dominate the field and supply an enormous amount of information concerning virus biology. In recent years, numerous fascinating high-resolution EM structures obtained by single-particle electron cryo microscopy (cryo-EM) were revealed for viral particles that possess icosahedral symmetry. However, no comprehensive three-dimensional analysis of complex viruses or viruses within cells has yet been achieved using EM. Recent developments in electron cryo-tomography render this a proficient tool for the analysis of complex viruses and viruses within cells in greater detail.

We established abnormal isoform of prion protein (PrPSc)-specific double immunostaining using mAb 132, which recognizes aa 119–127 of the PrP molecule, and novel PrPSc-specific mAb 8D5, which recognizes the N-terminal region of the PrP molecule. Using the PrPSc-specific double immunostaining, we analysed PrPSc in immortalized neuronal cell lines and primary cerebral-neuronal cultures infected with prions. The PrPSc-specific double immunostaining showed the existence of PrPSc positive for both mAbs 132 and 8D5, as well as those positive only for either mAb 132 or mAb 8D5. This indicated that double immunostaining detects a greater number of PrPSc species than single immunostaining. Double immunostaining revealed cell-type-dependent differences in PrPSc staining patterns. In the 22 L prion strain-infected Neuro2a (N2a)-3 cells, a subclone of N2a neuroblastoma cell line, or GT1-7, a subclone of the GT1 hypothalamic neuronal cell line, granular PrPSc stains were observed at the perinuclear regions and cytoplasm, whereas unique string-like PrPSc stains were predominantly observed on the surface of the 22 L strain-infected primary cerebral neurons. Only 14 % of PrPSc in the 22 L strain-infected N2a-3 cells were positive for mAb 8D5, indicating that most of the PrPSc in N2a-3 lack the N-terminal portion. In contrast, nearly half PrPSc detected in the 22 L strain-infected primary cerebral neurons were positive for mAb 8D5, suggesting the abundance of full-length PrPSc that possesses the N-terminal portion of PrP. Further analysis of prion-infected primary neurons using PrPSc-specific immunostaining will reveal the neuron-specific mechanism for prion propagation.

This paper explores a number of questions regarding optimal strategies evolved by viruses upon entry into a vertebrate host. The infected cell life cycle consists of a non-productively infected stage in which it is producing virions but not releasing them and of a productively infected stage in which it is just releasing virions. The study explores why the infected cell cycle should be so delineated, something which is akin to a classic “bang-bang control” or all-or-none principle. The times spent in each of these stages represent a viral strategy to optimize peak viral load. Increasing the time spent in the non-productively infected phase (τ1) would lead to a concomitant increase in peak viremia. However increasing this time would also invite a more vigorous response from Cytotoxic TLymphocytes (CTLs). Simultaneously, if there is a vigorous antibody response, then we might expect τ1 to be high, in order that the virus builds up its population and conversely if there is a weak antibody response, τ1 might be small. These tradeoffs are explored using a mathematical model of virus propagation using Ordinary Differential Equations (ODEs). The study raises questions about whether common viruses have actually settled into an optimum, the role for reliability and whether experimental infections of hosts with non-endemic strains could help elicit answers about viral progression.

A high percentage of cell lines are chronically infected with various mycoplasma species. The addition of antibiotics that are particularly effective against these contaminants to the culture medium during a limited period of time is a simple, inexpensive, and very practical approach for decontaminating cell cultures. Here, we examined the effectiveness of the new antimycoplasma compound Plasmocin that has been employed routinely to cleanse chronically infected cell lines. In a first round of treatment 45 out of 58 (78%) mycoplasma-positive cell lines could be cured. In a second attempt using back-up cryopreserved original cells, four additional cell lines were cured; thus, the overall cure rate was 84%. Even if the mycoplasma contamination was not eradicated by Plasmocin, the parallel treatment with several other antibiotics (Baytril, BM-Cyclin, Ciprobay, MRA, or MycoZap) led to the cure of all 58 cell lines. The successful decontamination was permanent as mycoplasmas were no longer detected at day +14 posttreatment and at later time points as examined by PCR which is the most sensitive and specific mycoplasma detection method. Collectively, our results highlight certain antibiotics as effective antimycoplasma reagents and support the therapeutic rationale for their use in the eradication of this notorious cell culture contaminant.

Infected cell protein 0 (ICP0) has been detected in the tear fluid of rabbits with herpetic keratitis. Here, we investigated whether ICP0 of herpes simplex virus 1 is detectable in the tear fluid of patients with herpetic epithelial keratitis.Seven patients with herpetic epithelial keratitis (age range, 51-76 years) and 11 healthy volunteers (age range, 48-85 years) were enrolled in the study. Tear fluid was collected with the use of Schirmer test strips and subjected to immunoblot analysis with antibodies to ICP0.ICP0 was not detected in the tear fluid of the healthy controls, whereas it was detected in 4 of the 7 patients with herpetic keratitis. The tear fluid of the 4 ICP0-positive patients was collected within 3 days of the onset of keratitis, whereas that of the ICP0-negative patients was obtained at least 7 days after disease onset.ICP0 was detected in the tear fluid of patients in the early phase of herpetic epithelial keratitis, but not in that of patients in the later stages of the disease nor in that of the healthy controls. ICP0 expression may thus be dependent on the disease phase.

The replication cycle of HIV proceeds within an infected cell and imaging techniques allow us to focus on the pathogen in this cellular environment. During recent years, both electron microscopy and fluorescence microscopy have evolved from methods providing two-dimensional still images to techniques that can resolve native, three-dimensional structures at resolutions down to approximately 20 Å, or allow direct real-time observation of dynamic intracellular events, respectively, thereby yielding numerous novel insights into HIV biology. Future technological developments are expected to narrow the gap between electron microscopy (high spatial and structural resolution, but no information about dynamics) and fluorescence microscopy (high temporal resolution and high throughput, but low spatial resolution), providing detailed views that will deepen our understanding of HIV–cell interactions.

A better understanding of the fundamental principles of host-pathogen interactions should enable us to develop new strategies to control disease and to eliminate or at least manage their causative agents. This is especially true for obligate biotrophic parasites like the rust fungi. One vital aspect in the field of obligate biotrophic host-pathogen interactions is the mobilization, acquisition and metabolism of nutrients by the pathogen. This includes transporters necessary for the uptake of nutrients as well as enzymes necessary for their mobilization and metabolism. In a broader sense effector molecules reprogramming the host or triggering the infected cell into metabolic shifts favorable for the pathogen also play an important role in pathogen alimentation.

Available online at www.sciencedirect.com ScienceDirect Physics of Life Reviews 11 (2014) 149–151 www.elsevier.com/locate/plrev Reply to comments CRISPR–Cas adaptive immunity and developments in CRISPR–Cas applications Reply to comments on “Diversity, evolution, and therapeutic applications of small RNAs in prokaryotic and eukaryotic immune systems” Edwin L. Cooper ∗ , Nicola Overstreet Laboratory of Comparative Immunology, Department of Neurobiology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095-1763, United States Received 13 December 2013; accepted 17 December 2013 Available online 21 December 2013 Communicated by M. Frank-Kamenetskii We appreciate the commentaries received from Stern [1], Pinti and Cossarizza [2], Plagens and Randau [3], Koonin [4], Wanner et al. [5], and Severinov [6], and their observations and insights, which we will now discuss. As is mentioned in many of the commentaries received, the emergence of knowledge about CRISPR–Cas systems marks an important shift in the mindset of immunology. For a long time, eukaryotic immune systems were viewed through the paradigm of self/not-self. This paradigm was rooted in clonal selection and the dual innate and adaptive model [7–9]. With the advent of the danger hypothesis, it became apparent that the self/not-self pattern was not im- pervious to upheaval [7,10]. Similarly, small RNA systems have shifted the perspective of immunology. When RNA systems were first discovered, they were seen as an exception to the suite of well-known protein-recognition adaptive immune defenses. However, in the words of Pinti and Cossarizza, “it is now clear even to us, human immunologists, that RNA-based defense mechanisms are the rule, and not the exception, and that the modern, adaptive immune system has been built on an ancient basement made by RNA” [2]. Stern similarly remarks that the wealth of RNA systems reveals the “general solutions to the problem of par- asites” [1]. The recognition of not-self motifs, infected cell death, and retained memory of past exposures are all mechanisms of immune defense that are observed across the tree of life [1]. Koonin likens small RNA defense mech- anisms to an idea that evolution found “ ‘too good’ to be abandoned” [4]. We agree that the pervasiveness of small RNA systems in prokaryotes and eukaryotes demonstrates the importance of these systems to life throughout the phy- logenetic tree, and speaks to the power of these types of systems. As Koonin states, “there seems to be underlying logic in their evolution that is both universal and simple” [4]. DOI of original article: http://dx.doi.org/10.1016/j.plrev.2013.11.002. DOIs of comments: http://dx.doi.org/10.1016/j.plrev.2013.11.004, http://dx.doi.org/10.1016/j.plrev.2013.12.001, http://dx.doi.org/10.1016/j.plrev.2013.11.012, http://dx.doi.org/10.1016/j.plrev.2013.12.002, http://dx.doi.org/10.1016/j.plrev.2013.12.003, http://dx.doi.org/10.1016/j.plrev.2013.11.015. * Corresponding author. 1571-0645/$ – see front matter © 2014 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.plrev.2013.12.011

Introduction: The objective of this study was to search for effective agents for the treatment of infections in animals or infected cell lines. Methods: The Homeopathic Basic Research experiments (HomBRex) database ( http://www.carstens-stiftung.de/hombrex ) on model biological systems in homeopathic research was searched. Eligible experiments were reviewed and analysed. Results: The database contains 48 eligible experiments published from 1832 to 2009. Causative pathogens were bacteria, fungi, viruses, proto- and metazoa. In the experiments, various parameters were observed and a large set of medicines was investigated. In eight of the 48 experiments, at least one of the investigated medicines was selected according to the similia principle. Nosodes and homeopathic complexes were investigated in 8 and 14 experiments respectively. Mice were the most often used host organisms (13 experiments). In 31 experiments at least one homeopathic medicine was found effective for treatment. Conclusion: The results of basic research experiments may invigorate new clinical trials that investigate complementary treatments for infectious diseases. However, all experiments reviewed here await replication and no clear-cut conclusion can be drawn regarding the transferability of in vitro results to in vivo outcomes.

Self assembly of viral biopolymers to nano-complexes forming virions during virus delivery from infected cell and reverse disintegration to virus entry into new cells play a crucial role in viral life cycle and in viral diseases. Therefore artificial instruments for selective counter intervention into these processes are dramatically required for the high effective antiviral protection. Hybrid macromolecular systems (HMS) rationally integrating heterogeneous structure-functional factors for selective recognition - inhibition of viruses (nano-objects) without detriment for cells (micro-objects) can become a molecular basis for cardinal progress in this area. Here we discuss approaches to design and current experimental results of synthesis, and antiviral selectivity evaluations of the HMS, based on combinations of polyelectrolyte-grafted components constructed on principles of mimicry and/or complementarity to viral targets or virus-sensitive cell receptors. Particularly, the HMS generations strongly inhibiting the human immunodeficiency virus (HIV) were created as platform to novel drug development against HIV/AIDS and other sexually transmitted infections.

Infection caused by pathogens kills millions of people every year. Comprehensive understanding of molecular pathogen-host interactions, i.e. the infectome, is one of the key steps towards the development of novel diagnostic, therapeutic and preventive strategies. In this quest, progress in high-throughput > technologies applied to pathogens, i.e. infectomics, opens new perspectives toward systemic understanding of perturbations induced during infection. Deciphering the pathogen-host system also relies on the analytical and predictive power of molecular systems biology and by developing in silico models taking into account the whole picture of the molecules and their interactions. In this context, we have reconstructed a prototype of the human virtual infected cell based on 30 years of intensive research in the field of molecular virology. This model contains more than one hundred viral infectomes, including major human pathogens (HCV, HBV, HIV, HHV, HPV) and has led to the generation of novel systems-level hypotheses that could be suitable for the development of innovative antiviral strategies based on the control of cellular functions.

Zusammenfassung Infizierte Zellkulturen eignen sich gut zur Gewinnung komplementbindender Antigene fur die Herpesvirus equi 1 (Rhinopneumonitis)-Serodiagnose. Das komplementbindende Antigen kann in der erforderlichen Konzentration aus der Zellphase mit hohen Dosen infizierter Kulturen gewonnen werden. Die Kulturantigene sind den herkommlichen Antigenen aus Lebern infizierter Hamster oder Organen abortierter Pferdefeten in ihren praktischen Eigenschaften uberlegen. In den eigenen Untersuchungen wurden Antigene aus BHK-Kulturen bevorzugt, weil sie einer heterologen Zellart entstammen, in befriedigender Konzentration herstellbar sind und bei ihrer Verwendung keine unspezifischen Reaktionen befurchtet werden mussen. Die Eignung komplementbindender Rhinopneumonitisantigene, gewonnen aus primaren Schweinenieren- und BHK-Kulturen, wurde in serologischen Routineuntersuchungen an Pferdeseren gepruft. Dabei wurde festgestellt, das die Verbreitung der Rhinopneumonitisinfektion im Raume Munchen-Oberbayern noch keinen rucklaufigen Trend aufweist. Summary Complement-fixing antibodies of herpes virus equi 1 (rhino-pneumonitis virus) from cell cultures and their use in serological diagnosis Infected cell cultures are very suitable for the production of complement-fixing antibodies for the serological diagnosis of herpes virus equi 1. The antigen can be obtained in the required concentration from the cell phase with high doses of infected cultures. The culture antigens are superior to the conventional antigens prepared from the livers of infected hamsters or from the organs of aborted equine foetuses. The authors prefer antigens from BHK cultures because they come from a heterologous cell species, they are available in suitable concentration and nonspecific reactions are unlikely. The quality of complement-fixing rhino-pneumonitis antigens produced from primary pig kidney and BHK cultures was tested in routine serological studies on horse sera. The results showed that there is still no tendency for regression in the spread of rhino-pneumonitis infection in the Munich-Upper Bavaria area. Resume Antigenes du virus herpes equi 1 (rhinopneumonnitisvirus), fixant le complement, obtenus en cultures de cellules; leur application dans le diagnostic serologique Des cultures de cellules infectees conviennent fort bien a la preparation des antigenes fixant le complement pour le diagnostic du virus herpetique equi 1 (rhinopneumonitis). On obtient l'antigene fixant le complement, a la concentration requise, a partir de la phase cellulaire de cultures infectees a fortes doses. Les antigenes de cultures sont superieurs aux antigenes conventionnels prepares a partir de foies de hamsters infectes ou d'organes de foetus equins avortes, grâce a leurs proprietes pratiques. Dans nos recherches personelles, nous preferons les antigenes cultures BHK, parce qu'ils proviennent d'une espece cellulaire heterologue, qu'on en obtient des concentrations satisfaisantes et que utilisation n'entraine pas de reactions non specifiques. La qualite des antigenes de la rhinopneumonie, fixant le complement, prepares a partir de cultures primaires de reins de porcs et de cultures BHK, est testee dans des exames serologiques de routine sur des serums equins. On trouve que la propagation de l'infection de la rhinopneumonie ne manifeste encore aucune tendance a la regression dans la region de Munich — Haut Baviere. Resumen Antigenos fijadores del complemento del virus herpetico equi 1 (virus de la rinopneumonitis) a partir de cultivos celulares y su aplicacion en el diagnostico serologico Los cultivos celulares infectados resultan muy apropiados para obtener antigenos fijadores del complemento destinados el serodiagnostico del virus herpetico equi 1 (rinopneumonitis). El antigeno fijador del complemento se puede conseguir en la concentracion precisa de la fase celular de cultivos infectados con dosis elevadas. Los antigenos celulares son superiores en sus propiedades practicas a los antigenos inveterados de higados de hamsters infectados o de organos de fetos abortados de yegua. En los estudios propios se prefirieron los antigenos de cultivos BHK (rinones de hamsters bebes), ya que proceden de una especie celular heterologa, se pueden elaborar en concentracion satisfactoria y no se precisan temer reacciones inespecificas con su empleo. La idoneidad de los antigenos fijadores del complemento de la rinopneumonitis, obtenidos a partir de cultivos primarios de rinones porcinos y BHK, se contrasto en pesquisas serologicas de rutina con sueros sanguineos equinos. De esta forma se pudo comprobar que la difusion de la infeccion rinopneumonitica aun no presenta ninguna tendencia retrograda en el territorio de Munich-Alta Baviera.

Bacteria use a variety of mechanisms during infection to ensure their survival including the delivery of virulence factors via a type III secretion system into the infected cell. The factors exhibit diverse activities that in many cases mimic eukaryotic mechanisms used by the host to defend against infection. Herein we describe a class of effectors that use post-translational modifications, some reversible and others irreversible, to manipulate host signaling systems to subvert the host response.

A rapid and efficient procedure for the purification of myxoma virus DNA from infected cell cultures is described. The traditional method used for recovery of myxoma virus DNA involves multiple freeze-thawing cycles to disrupt cells and release virions followed by ultracentrifugation to concentrate virions for DNA extraction. Freeze-thaw cycles are time consuming and reduce viral titers, while ultracentrifugation steps limit the number of samples that can be processed at one time, reducing efficiency. In this report an optimized method circumventing the time-consuming techniques and replacing them with rapid, efficient steps adequate for the processing of larger numbers of samples is described. The traditional method was compared with the optimized protocol, which was found to be more efficient in terms of time required to complete the process and in the quantities of DNA purified.

Interactions between bacteriophage proteins and bacterial proteins are important for efficient infection of the host cell. The phage proteins involved in these bacteriophage-host interactions are often produced immediately after infection. A survey of the available set of published bacteriophage-host interactions reveals the targeted host proteins are inhibited, activated or functionally redirected by the phage protein. These interactions protect the bacteriophage from bacterial defence mechanisms or adapt the host-cell metabolism to establish an efficient infection cycle. Regrettably, a large majority of bacteriophage early proteins lack any identified function. Recent research into the antibacterial potential of bacteriophage-host interactions indicates that phage early proteins seem to target a wide variety of processes in the host cell - many of them non-essential. Since a clear understanding of such interactions may become important for regulations involving phage therapy and in biotechnological applications, increased scientific emphasis on the biological elucidation of such proteins is warranted.

A counterimmunoelectrophoretic method for quantitative determination of antibodies against measles virus nucleocapsid is described. Unfractionated material from measles virus infected cell cultures was used as antigen, diluted to give only a nucleocapsid-specific precipitate. Purified nucleocapsid and a rabbit hyperimmune serum against this antigen was used to establish the specificity of the test. The measles virus specific antibody titres determined by the method were comparable to those found in nucleocapsid complement fixation tests. It is concluded that the technique described offers a simple and sensitive method to determine nucleocapsid specific antibodies.

A mathematical model for the effect of Reverse Transcriptase (RT) Inhibitor on the dynamics of HIV is proposed and analyzed. Further, with help of numerical simulations, the relation between efficacy of administered drug, the total number of virus particles emitted from the infected cell and the transition period is also discussed.

Genome replication of reovirus occurs in cytoplasmic inclusion bodies called viral factories or viroplasms. The viral nonstructural protein μNS, encoded by genome segment M3, is not a component of mature virions, but is expressed to high levels in infected cells and is concentrated in the infected cell factory matrix. Recent studies have demonstrated that μNS plays a central role in forming the matrix of these structures, as well as in recruiting other components to them for putative roles in genome replication and particle assembly.

In this study, the infection cycle of bacteriophage Qbeta was investigated. Adsorption of bacteriophage Qbeta to Escherichia coli is explained in terms of a collision reaction, the rate constant of which was estimated to be 4x10(-10) ml/cells/min. In infected cells, approximately 130 molecules of beta-subunit and 2x10(5) molecules of coat protein were translated in 15 min. Replication of Qbeta RNA proceeded in 2 steps-an exponential phase until 20 min and a non-exponential phase after 30 min. Prior to the burst of infected cells, phage RNAs and coat proteins accumulated in the cells at an average of up to 2300 molecules and 5x10(5) molecules, respectively. An average of 90 infectious phage particles per infected cell was released during a single infection cycle up to 105 min.

The role of autochthonous viruses in the regulation of bacterioplantkon abundance and production was studied in the Rybinsk Reservoir. During the ice-free period, the number of virus-like particles varied within the range of (11.0–57.4) × 106 particles/ml. The virus to bacterioplankton abundance ratio ranged within 3.0–9.4. From 4 to 25% of bacterioplankton was infected by phages. A single infected cell contained up to 80 mature virus particles. The phage-induced bacterioplankton mortality in different parts of the reservoir constituted 3.7–41.8% (22.5% on average) of bacterioplankton daily production. Heterotrophic flagellates grazed from 7.6 to 68.8% (27.5% on average) of the daily bacterial production. Thus, along with flagellates, viruses are an important factor controlling bacterioplankton development in the reservoir.

Influenza virus infection results in the activation of a variety of intracellular signaling responses. With regard to the function of these responses, the overall picture that has emerged suggests that most of the signaling events are initiated as a cellular response to defend the invading pathogen. While on the one hand influenza viruses have evolved strategies to keep these responses in a tolerable limit, there is accumulating evidence that the virus has also acquired the capability to exploit the remaining activities to ensure efficient replication. Here we will summarize the current knowledge on influenza virus-induced signaling processes and how these pathogens take advantage of some of these activities within the infected cell to support its propagation.

Cell-to-cell viral infection, in which viruses spread through contact of infected cell with surrounding uninfected cells, has been considered as a critical mode of virus infection. However, since it is technically difficult to experimentally discriminate the two modes of viral infection, namely cell-free infection and cell-to-cell infection, the quantitative information that underlies cell-to-cell infection has yet to be elucidated, and its impact on virus spread remains unclear. To address this fundamental question in virology, we quantitatively analyzed the dynamics of cell-to-cell and cell-free human immunodeficiency virus type 1 (HIV-1) infections through experimental-mathematical investigation. Our analyses demonstrated that the cell-to-cell infection mode accounts for approximately 60% of viral infection, and this infection mode shortens the generation time of viruses by 0.9 times and increases the viral fitness by 3.9 times. Our results suggest that even a complete block of the cell-free infection would provide only a limited impact on HIV-1 spread. DOI: http://dx.doi.org/10.7554/eLife.08150.001, eLife digest Viruses such as HIV-1 replicate by invading and hijacking cells, forcing the cells to make new copies of the virus. These copies then leave the cell and continue the infection by invading and hijacking new cells. There are two ways that viruses may move between cells, which are known as ‘cell-free’ and ‘cell-to-cell’ infection. In cell-free infection, the virus is released into the fluid that surrounds cells and moves from there into the next cell. In cell-to-cell infection the virus instead moves directly between cells across regions where the two cells make contact. Previous research has suggested that cell-to-cell infection is important for the spread of HIV-1. However, it is not known how much the virus relies on this process, as it is technically challenging to perform experiments that prevent cell-free infection without also stopping cell-to-cell infection. Iwami, Takeuchi et al. have overcome this problem by combining experiments on laboratory-grown cells with a mathematical model that describes how the different infection methods affect the spread of HIV-1. This revealed that the viruses spread using cell-to-cell infection about 60% of the time, which agrees with results previously found by another group of researchers. Iwami, Takeuchi et al. also found that cell-to-cell infection increases how quickly viruses can infect new cells and replicate inside them, and improves the fitness of the viruses. The environment around cells in humans and other animals is different to that found around laboratory-grown cells, and so more research will be needed to check whether this difference affects which method of infection the virus uses. If the virus does spread in a similar way in the body, then blocking the cell-free method of infection would not greatly affect how well HIV-1 is able to infect new cells. It may instead be more effective to develop HIV treatments that prevent cell-to-cell infection by the virus. DOI: http://dx.doi.org/10.7554/eLife.08150.002

In high risk forms, human papillomaviruses (HPV) can either induce or promote cancerous lesions, especially cervical cancer which is considered the second most common cancer in the women worldwide. HPV life cycle is tightly linked to the infected cell differentiation program and its evolution is strictly joined to the switch between the early and the late viral polycistronic promoters.The aim of this study is to develop a novel mathematical model which collects and structures the available biologic knowledge on the early promoter regulation for HPV in episomal form. The model includes the main regulation by E2 viral protein as well as a novel discovered co-regulation function mediated by the viral E1 protein. Only by including both E2 and E1 regulatory effect the model is able to correctly predict the temporal behaviour of the early promoter switching off. A possible use of the model as in silico tool to evaluate new antiviral therapies is discussed.