Influenza epidemics are the cause of three to five million cases of severe illness every year and approximately 250,000 to 500,000 of these cases are fatal. Epidemics occur during autumn and winter in regions with a temperate climate, while in some tropical countries influenza viruses circulate throughout the year with one or two peaks during the rainy seasons. Mainly the young, elderly and subjects with chronical medical conditions are at risk for developing severe disease after seasonal influenza virus infection. Therefore, the World Health Organization (WHO) recommends annual vaccination of these subjects, which is an effective measure to protect them against influenza and its complications.
The genome of influenza viruses consists of eight gene segments of negative sense RNA and since these viruses lack proofreading activity during their replication, they can accumulate mutations under selective pressure. This way, influenza viruses can escape from recognition by virus-neutralizing antibodies that are induced by previous infections or vaccinations. Indeed, the highest degree of variations is observed in the antigenic sites of the hemagglutinin against which virus neutralizing antibodies are directed. As a result of this antigenic variation, the influenza vaccine that contains components of three currently circulating influenza viruses (A/H1N1, A/H3N2 and B viruses) has to be updated almost every year to match the circulating strains. Since the selection of the vaccine strains and vaccine production has to be carried out before the start of the influenza season, there is some uncertainty in this prediction and mismatches do occur occasionally. In addition to the small gradual antigenic changes of currently circulating influenza virus strains (antigenic drift), occasionally new influenza viruses of novel subtypes are introduced into the human population. The subtypes of these viruses are defined by the envelope glycoproteins of these viruses, the hemagglutinin (HA) and the neuraminidase (NA). Wild aquatic birds are the natural reservoir of all subtypes of influenza from which there is spillover to other (domestic) birds and mammalian species, like pigs, horses and men.
Because antibodies against these viruses are virtually absent in the human population, these viruses may cause pandemic outbreaks of influenza affecting a substantial proportion of the human population. In the last century, three pandemics occurred, which were caused by influenza A viruses of the H1N1, H2N2 and H3N2 subtypes. Recently, influenza A viruses of swine origin have caused the first pandemic of the 21st century. These new pandemic viruses are the result of the exchange of gene segments originating from human, classical swine and avian-like influenza viruses and have emerged and spread worldwide within a few months. As of 30 December 2009 at least 12220 people have been killed due to infection with the influenza A/H1N1(2009) virus. Since not all fatal cases are reported, the real number of fatal cases is most likely much higher.
The current pandemic caused by the new influenza A(H1N1) virus and the current pandemic threat caused by the highly pathogenic avian influenza A viruses of the H5N1 subtype have renewed the interest in the development of vaccines that can induce broad protective immunity. Preferably, vaccines not only provide protection against the homologous strains, but also against heterologous strains, even of another subtype. This paper describes viral targets and the arms of the immune response involved in protection against influenza virus infections such as antibodies directed against the hemagglutinin, neuraminidase and the M2 protein and cellular immune responses directed against the internal viral proteins.
Among the negative RNA viruses, ambisense RNA viruses occupy a distinct niche. Ambisense viruses contain at least one ambisense RNA segment, i.e. an RNA that is in part of positive and in part of negative polarity. Because of this unique gene organization, one might expect ambisense RNA viruses to borrow expression strategies from both positive and negative RNA viruses. However, they have little in common with positive RNA viruses, but possess many features of negative RNA viruses. Transcription and/or replication of their RNAs appear generally to be coupled to translation. Such coupling might be important to ensure temporal control of gene expression, allowing the two genes of an ambisense RNA segment to be differently regulated. Ambisense viruses can infect one host asymptomatically and in certain cases, they can lethally infect two hosts of a different kingdom. A possible model to explain the differential behavior of a given virus in different hosts could be that perturbation of the translation machinery would lead to differences in the severity of symptoms.
The ambisense coding strategy is an unusual way of encoding genes that presumably allows the virus to temporally control expression of the viral proteins, in particular if coupling of translation to transcription enhances the level of vc-encoded versus v-encoded protein expression. In any event, translation itself and/or translational control appear to play an important role in regulation of gene expression of ambisense viruses. Ambisense viruses have two hosts in which they can replicate. In their vector or reservoir host, infection is usually asymptomatic. However, in another host, multiplication of the virus can be lethal. Replication/transcription experiments in different host cell types would be helpful to shed further light on the differences observed in different hosts. At present, there are many complementary ways to study ambisense virus replication/ transcription such as cell culture, in vitro assays and reverse genetics systems. Since ambisense viruses are the meeting point of different viral families and are able to replicate in different hosts whether plants or animals and have different behaviors depending on the host, it would be particularly important to better understand the complex replicative cycle of ambisense viruses, in order to find the means to alleviate the lethal aspects of these pathogens.
Traditional lab tests for disease diagnosis can be too expensive and cumbersome for the regions most in need. George Whitesides’ ingenious answer is a foolproof tool that can be manufactured at virtually zero cost, as shown in this video:
Swarming is flagella-driven bacterial group motility over a surface, which is observed in the laboratory on media solidified with agar. The percentage of agar is critical for enabling swarming. Some bacteria like Vibrio parahaemolyticus and Proteus mirabilis can swarm readily on higher percentage agar, whereas others like Salmonella, Escherichia coli, Serratia, Pseudomonas, and Bacillus swarm only on lower percentage agar. Hard-agar swarmers differentiate into specialized swarm cells that are elongated and have increased flagella. Medium-agar swarmers generally do not display a similar differentiated morphology. In many of the latter class of swarmers (e.g. Serratia, Pseudomonas, Bacillus), movement is enabled by powerful extracellular surfactants whose synthesis is under quorum-sensing control. Surfactants lower surface tension and allow rapid colony expansion. Salmonella and E. coli do not appear to make such surfactants.
Swarming bacteria exhibit adaptive resistance to multiple antibiotics. Analysis of this phenomenon has revealed the protective power of high cell densities to withstand exposure to otherwise lethal antibiotic concentrations. This paper shows that that high cell densities promote bacterial survival, even in a nonswarming state, but that the ability to move, as well as the speed of movement, confers an added advantage, making swarming an effective strategy for prevailing against antimicrobials. There is no evidence of induced resistance pathways or quorum-sensing mechanisms controlling this group resistance, which occurs at a cost to cells directly exposed to the antibiotic. This work is relevant to the adaptive antibiotic resistance of bacterial biofilms.
Coldwater and tropical fish are the third most popular pet in the UK after cats and dogs. Over 3 million homeowners have a pond in their garden and many of these are stocked with fish, some of which, like koi carp, are very expensive. As Keith Way describes in this article in Microbiology Today (pdf) a whole host of viruses are in the environment just waiting to infect them with harmful diseases:
With the discovery of non-filterable disease agents, or viruses, in the late 19th century there came a greater realization of the role that viruses may play in infectious diseases of fish. However, the breakthrough for fish virology came with the general developments in virological techniques that blossomed in the 1950s and 60s. In particular, visualization of viruses by electron microscopy, improvements in protein and nucleic acid analysis and, most significantly, the isolation of viruses on continuous (immortal) fish cell lines. At the same time, aquaculture around the world developed in the 1960s and 70s, and farming of fish and fish-keeping rapidly increased. With these developments and, more recently, the global increase in trade in ornamental fish there has been an increase in new diseases and the emergence of serious virus diseases. Viruses that have caused serious but isolated disease outbreaks in cyprinid species and some ictalurid (catfish) species, and may affect coldwater ornamental fish, include aquareoviruses, coronaviruses, poxviruses and iridoviruses. More serious disease epidemics in ornamental species have been caused by rhabdoviruses and herpesviruses.
Nearly half of adolescents admitted to two public hospitals in Zimbabwe are HIV positive according to a new paper in PLoS Medicine. This study examines the causes of unselected acute hospitalization in adolescents, and serves to highlight the growing crisis of HIV acquired at birth in teenagers and young adults in the developing world. Each 10-18 year old participant completed a questionnaire about themselves and their health and underwent standard investigations, including HIV testing. Nearly half of participants were HIV positive; they were more likely to be stunted, to have pubertal delay, and to be maternal orphans or have an HIV-infected mother than HIV-negative adolescents. 69% of HIV-positive participants were admitted to hospital because of infections such as tuberculosis or pneumonia whereas only 19% of the HIV-negative participants were admitted for infections. 22% of the HIV-positive participants died while in hospital compared to only 7% of the HIV-negative participants.
Few studies have addressed the prevalence of perinatally-acquired HIV in older children and adolescence, perhaps because it was thought that children infected at birth were unlikely to survive beyond 5 years of age. Additionally, while the researchers assessed causes of hospitalization such as infectious disease or chronic underlying disease, they did not assess underlying mental health conditions. In the developed world, the most common reasons for psychiatric hospitalization for HIV-infected children were for depression or behavioral disorders and calls for the impact of death and chronic ill health of caregivers or siblings on HIV-infected adolescents in the developing world require investigation.
Should we destroy the remaining laboratory stocks of smallpox virus?
Now that the 20th century has passed into the domain of history books, we can retrospectively begin to assess the relative contributions that the many advances in the realm of infectious disease have actually made to public health in general. At the top of this virtuous list will surely be the discovery of antibiotics in the 1930s and the use of vaccination to eradicate smallpox as an extant human disease in the 1960s and 1970s. As clearly pointed out in a recent book by D. A. Henderson, one of the leaders of the global smallpox eradication program, this task of ridding Homo sapiens from the curse of this ancestral disease was neither easy nor without controversy. In fact, the history of the many consequences of smallpox on humankind reads like a long litany of human misery and calamitous events, but is juxtaposed with the more noble accomplishments that began with the discovery of vaccination by Jenner in 1798 and culminated with the World Health Organization (WHO) certifying the world free of smallpox in 1980. With this singular accomplishment, as many as 60–100 million individuals who would have been predicted to die of smallpox have been spared from a truly gruesome death. Nevertheless, the narrative of smallpox did not stop with its eradication as a pandemic human disease. Instead, we find ourselves still wrestling with an issue that intermingles public health policy, philosophy, national security, and bioterrorism, and affects our perceptions of research ethics with extreme pathogens in general. It boils down to a not-so-simple question: What exactly should the Victor do with the Vanquished?
Most bacteria contain in their envelope a peptidoglycan (or “murein”) layer which protects the cell from rupture as a result of osmotic pressure (turgor) of the cytoplasm and which maintains the specific shape (sphere, rod, spiral or other) of the bacterial cell. Although the chemical composition varies in different species, peptidoglycan is always made of glycan strands that are crosslinked by short peptides. Characteristic structural features include N-acetylmuramic acid (MurNAc), d-amino acids and unusual amide bonds. Many important questions on the structure and growth of the sacculus remain unanswered. Of particular interest is the architecture of peptidoglycan, the knowledge of which is needed to understand the mechanism(s) of enlargement of the sacculus in growing and dividing cells.
A crucial feature of the architecture of peptidoglycan is the orientation of the glycan strands and peptides with regard to surface and axis of the cell. However, the large size, structural heterogeneity and flexibility of the peptidoglycan sacculi preclude crystal formation and hence determination of the crystal structure. Furthermore, the glycan strands and peptides cannot be seen by conventional electron microscopy because their dimensions are of the same scale as the inevitable staining and fixation artifacts. Thus, current models of the architecture are based on chemical and biophysical data which, however, are limited to just a few species. Two mutually exclusive models are currently being discussed: the classical “layered” model in which both the glycan strands and peptide crosslinks run parallel (horizontal) to the cytoplasmic membrane, and the “scaffold” model in which the glycan strands run perpendicular to the membrane and the peptide crosslinks run parallel to the membrane. The existence of these fundamentally different models and the arguments about them have had one very positive effect: structural biologists are beginning to regain their interest in this problem utilizing current technologies and new methods.
In 2008, two important articles on the architecture of peptidoglycan were published. The first describes the architecture of sacculi isolated from Gram-negative species analyzed by electron cryotomography. The second reports on the architecture of peptidoglycan isolated from the Gram-positive, rod-shaped Bacillus subtilis as observed by atomic force microscopy (AFM). Although the new data support a layered architecture in Gram-negative bacteria, the situation appears to be more complex in B. subtilis. The data suggest that neither of the two models apply. This article summarizes the state of knowledge of peptidoglycan, discusses current models for Gram-negative and Gram-positive bacteria and notes the many unanswered questions about the architecture of peptidoglycan which remain.
Influenza epidemics are the cause of three to five million cases of severe illness every year and approximately 250,000 to 500,000 of these cases are fatal. Epidemics occur during autumn and winter in regions with a temperate climate, while in some tropical countries influenza viruses circulate throughout the year with one or two peaks during the rainy seasons. Mainly the young, elderly and subjects with chronical medical conditions are at risk for developing severe disease after seasonal influenza virus infection. Therefore, the World Health Organization (WHO) recommends annual vaccination of these subjects, which is an effective measure to protect them against influenza and its complications.
