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Using a new method to test potential pandemic flu strains, scientists have created a virus that contains genes from human and bird flus and found it lacks what it takes to cause a pandemic.

The researchers combined genes from a human flu strain, H3N2, and the H5N1 bird flu strain that emerged in Hong Kong in 1997, which is an earlier version of the deadly strain that is circulating in parts of Asia, Africa and Europe. They found that in animal experiments, the mixed virus lacks “the key property that predicts pandemic spread.”

But experts say other gene combinations or mutations could turn H5N1 into a pandemic strain.

“We are far from out of the woods in H5N1 on a global scale,” Julie Gerberding, director of the Centers for Disease Control and Prevention, said in a briefing on the study. It was published Monday in the Proceedings of the National …

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ABSTRACT

Virus capsids and crystalline surfactant vesicles are two examples of self-assembled shells in the nano- to micrometer size range. Virus capsids are particularly interesting since they have to sustain large internal pressures while encapsulating and protecting the viral DNA. We therefore study the mechanical properties of crystalline shells of icosahedral symmetry on a substrate under a uniaxial applied force by computer simulations. We predict the elastic response for small deformations, and the buckling transitions at large deformations. Both are found to depend strongly on the number of elementary building blocks N (the capsomers in the case of viral shells), the Föppl-von Kármán number γ (which characterizes the relative importance of shear and bending elasticity), and the confining geometry. In particular, we show that whereas large shells are well described by continuum elasticity-theory, small shells of the size of typical viral capsids behave differently already for small deformations. Our results are essential to extract quantitative information about the elastic properties of viruses and vesicles from deformation experiments.

INTRODUCTION

The formation of regular polyhedra is a frequently encountered strategy of nature to optimize self-assembled structures. Microscopic boron clusters (1), mesoscopic surfactant vesicles (2), vesicles formed from wheel-shaped molybdenum clusters (3), as well as about half of all known spherical virus particles (4) are all small self-assembled structures that have an underlying icosahedral symmetry. It is interesting that the overall three-dimensional structure of many viruses is so similar whereas they are built from different protein subunits. Two illustrative examples of well-known viruses are the tomato bushy stunt virus and the bacteriophage φ29. Tomato bushy stunt virus was the first virus for which the icosahedral structure was predicted (5) and later confirmed by virus crystallography (6). This virus consists of 180 protein subunits that aggregate into a virus shell of ~34-nm diameter that encapsulates the viral genome. The typical contact energy between the different subunits is in the range of 100-400 kJ/mol, which corresponds to several tens of k^sub B^T per bond. The bacteriophage φ29 is a small bacteria-infecting virus consisting of a head of 235 gp8 protein subunits-forming two icosahedral end caps and a cylindrical equatorial region-and a long flexible tail (7). It has been demonstrated by DNA packaging experiments using optical tweezers (8) that the genome of this virus is very tightly packed into the capsid by a molecular motor, leading to an internal pressure of ~50 atm (9). This high pressure results in a formidable injection force when the virus infects a host cell. Therefore, virus capsids must be mechanically very strong.

Different types of protein subunits aggregate under the appropriate conditions (ionic strength, pH, temperature) into stable virus capsids. However, the mechanically coherent shell often consists of only a single kind of protein subunit. This process of spontaneous aggregation is very similar to micellization in surfactant solutions and can be largely understood using self-assembly theory (10-12). Recently, several groups studied the formation of these icosahedral particles by computer simulation (13-15). More complex shapes can be obtained by introducing a spontaneous curvature that competes with the ratio of bending and stretching energy (13,16). The origin of the stability of the icosahedral shape as an approximation to a sphere lies in the fact that any regular triangulation of a smooth sphere requires an excess of at least 12 fivefold disclinations (17). Caspar and Klug (18) first showed that the organization of proteins in the viral shell is such that a few proteins each form hexavalent and pentavalent morphological units, the capsomers. Furthermore, the icosadeltahedral structure of a virus shell can then be characterized by two integers p and q such that the number of vertices (i.e., of the morphological units) is N = 10T + 2, the number of triangles is N^sub T^ = 20T, and the number of subunits is N^sub S^ = 3N^sub T^, where T = p^sup 2^ + pq + q^sup 2^, the so-called T-number of the virus. For many virus particles, relatively few subunits are involved so that T and N^sub T^ are small.

Given the intrinsic strength of the virus capsids that follows from experiments (8) as well as from calculations of protein-protein interactions (19), it is important to probe the mechanical properties of viruses directly by means of singleparticle experiments. The main question is then how to relate the experimentally accessible observable to the elastic constants of the virus capsid. Recently, controlled experiments using scanning-force microscopy have been used to measure the mechanical properties of (empty) bacteriophage φ29 capsids (20). Similar measurements on hollow spherical polyelectrolyte capsules (21) were reported in Lulevich et al. (22) and Fery et al. (23).

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Avian influenza virus sequences will be made accessible to the entire scientific community through an initiative of OFFLU, the joint network of expertise on avian influenza formed by the Food and Agriculture Organization (FAO) and the World Organization for Animal Health (OIE).
With this gesture OFFLU reiterates its call to the world’s scientists, international organisations and countries for a global sharing of virus strains and sequences.

OFFLU was launched by the FAO and OIE in April 2005. Since then, the organisation has been mainly working on …

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During a keynote speech at the GeoTec Event, Canadian researcher Tom Koch examined the role of mapping for analysis and suggested that humans are the primary vector for the spread of West Nile Virus. The author of Cartographies of Disease: Maps, Mapping and Medicine currently is using mapping to critique theories of West Nile Virus and understand its ecology.

"The reflex assumption has been that this is a simple virus with an avian reservoir and mosquito vectors," said Koch. "All other species infected are assumed to be peripheral to the disease’s spread and …

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When word spreads of a devastating computer virus making rounds via the Internet, businesses worldwide scramble to circumvent any hard drive-stripping, system-confounding cyber-bugs identified by those unfortunate enough to have suffered their wrath. If they are prudent, businesses likewise will heed warnings a and prepare for, a potential biological threat in the form of an incipient avian influenza virus that hasappeared inparts of Asia, Europe, and the Middle East.

Public health officials don’t want to be alarmist. In order for an actual pandernic to play out, human-to-human transmission of the virus be documented. To date, observation of such transmission has been so limited as to be statistically nonexistent. However, officials would like to make foresight 20/20 and avoid any worst-case scenarios that could ravage the country’s population - and its economy.

The disease in question, Avian Influenza A (also known as the H5N1 virus), actually is quite rare in humans. Widely known as the “bird flu,” it occurs naturally in wild and domesticated birds and can be lethal to bird populations. The highly contagious virus is transmitted through the saliva, mucus, and excretions of infected birds. Nonetheless, incidences of bird-to-human transmission - most probably when a human has come into direct contact with diseased poultry or droppings from an infected bird - have warranted precaution.

Federal Health and Human Services (HHS) Secretary Mike Leavitt in December 2005 alerted state governors of pandemic flu concerns and enlisted their help in getting word out within their states. Leavitt pledged that the HHS would hold pandemic planning summits in all 50 states to improve their level of preparedness. Leavitt’s multi-state alert included a tri-agency letter to business leaders, which is excerpted below:

We are writing to you today on behalf of the departments of Commerce, Health and Human Services, and Homeland Security to enlist your support in encouraging preparedness for such an event within the business community. We are requesting that you, as a business leader, focus on the need for planning within your organization for the possibility of an influenza pandemic.

It is important to note from the outset that there is not a human influenza pandemic at this time, nor can we say that a pandemic is imminent. However, as the President has noted, a new strain of influenza virus (H5N1) has been found in birds in Asia, and it has been shown that is virus can infect humans. If the virus mutates in certain ways, it is possible that it could lead to a pandemic. Because the threat does exist, we think it important to be for you knowledgeable about the risks associated with the threat of an influenza pandemic and, in turn, to be adequately prepared for the possibility pandemic that would have significant social a economic costs.

In order to ensure maximum preparedness, your business should develop specific plans for the ways that you would protect your employees and maintain operations during a pandemic. Companies that provide critical infrastructure services, such as power and telecommunications, also have a special responsibility to plan for continued operation in a crisis and should plan accordingly. As with any catastrophe, having a contingency plan is essential.

On March 2, 2006, the state of South Carolina, HHS, and other federal agencies conducted a Pandemic Planning Summit at which Gov. Mark Sanford (pictured above, center) joined Leavitt in signing a pandemic planning resolution for the state.

In January 2006, Leavitt announced that $100 million of an emergency $350 million congressional appropriation for combating pandemic influenza will be distributed to states, based on a formula adjusted for population, to help with pandemic planning activities. South Carolina will receive $1.5 million of that distribution.

“The first mention of influenza in South Carolina appeared on September 27, 1918, in the state’s public health reports,” Leavitt said in his opening remarks for the South Carolina Summit. “Four days later, a telegram reported 1,500 cases in the state. By the end of the month, an estimated 80,000 cases had occurred, resulting in some 3,000 deaths.

“Schools and businesses were closed; public gatherings were banned. Even the state Supreme Court shut its doors. The wearing of gauze masks was strongly encouraged, and institutions with space to spare, such as the University of South Carolina, became auxiliary hospitals….

“When it comes to pandemics, there is no rational basis to believe that the early years of the 21st century will be different than the past. If a pandemic strikes, it will come to South Carolina.”

According to the federal Centers for Disease Control (CDC), the H5N1 I strain has caused the largest number of cases of severe disease and death among humans. From January 2003 to July 2006, the World Health Organization (WHO) had confirmed a total of 229 cases of H5N1 infection in humans and 131 deaths. By far, the highest incidences had occurred in Vietnam and Indonesia.

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CORPORATE IT UPDATE-(C)1995-2006 M2 COMMUNICATIONS LTD

BlackSpider Technologies, the on-demand security service of SurfControl plc, has revealed that the number of e-mail-borne viruses has risen for the first time in seven months.

According to the company, in June 2006 the number of e-mail-borne viruses decreased to a record low, accounting for 0.68% of all e-mails seen by the company. In July 2006 this figure had increased to 0.93%.

The ten most common malware sent in July 2006 were, in order: Trojan-Spy.HTML.Bankfraud.od, accounting for 20% of all malware seen by BlackSpider; W32.Netsky.P; W32.Beagle!zip; Trojan-Spy.HTML.Bankfraud.pd; W32.Blackmal.E; W32.Netsky.D; W32.Mydoom.M; Trojan-Spy.HTML.Fraud.l; W32.Mytob.AG; and Exploit-MIME.gen.c, the company claims.

((Comments on this story may be sent to info@m2.com))

COPYRIGHT 2006 M2 Communications Ltd.
COPYRIGHT 2008 Gale, Cengage Learning

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Sir,

Japanese encephalitis (JE) is a mosquito borne viral disease that affects central nervous system and can cause severe complications and even death1. JE is a major seasonal health problem in many rural areas in India and other parts of Asia with 30-50,000 cases reported annually2,3. The onset of symptoms in JE infection is characterized by fever, headache, vomiting followed by nuchal rigidity, focal neurological signs, and convulsions and altered sensorium3. Case fatality rates vary from 20-40 per cent in children4. Nearly one half of the survivors have significant neurologic sequelae. In 1952, neutralizing antibodies to JE virus were found to exist in patients at several places in India like Nagpur district of Maharastra, Chingleput district of Tamil Nadu, Gujarat and Andhra Pradesh5. In Uttar Pradesh first outbreak occurred in 1978 in north eastern district2. A study from Lucknow suggested that disease was endemic in the north eastern districts of U.P. including Gorakhpur, Deoria, Ajamgarh, Basti, Gonda, Balia, Faizabad, and Lakhimpur KhM6-8.

This study was conducted in the Virology section of Post Graduate Department of Microbiology, King George’s Medical University, Lucknow during March and June 2005. A total of 57 consecutive cases suspected to have acute encephalitis were included in the study. Of these, 35 patients were from paediatric age group and 18 were adults. With the help of physician in-charge a detailed history was taken and physical examination was performed according to predesigned proforma. A careful record of patients’ progress in the hospital was maintained during his/her stay. Two blood samples (5 ml) were taken, one at the time of admission and another 8 days later. Paired sera could be collected only from 13 cases. Only single serum sample during acute phase of illness was collected from 44 patients. Thus, a total of 70 serum samples were subjected to haemagglutination inhibition (HI) test to established laboratory diagnosis of JE3. Blood was allowed to clot at room temperature and serum was separated by centrifugation. Kaolin treatment of the sera was done and samples were stored at -20γC. After collection of duck RBC and titration of the antigen, HI test was done for antibody titre. JE antigen control and RBC control were used to see for button and carpet formation. Haemagglutination titre was taken as highest dilution of serum which showed inhibition of agglutination. Four-fold increase in antibody titre was considered as positive HI test.

Of the 13 paired samples, seven were positive. Of these, in four samples diagnosis was made by fourfold or higher rise in HI antibody titre. In two samples, there was four-fold or more fall in HI antibody titre. One sample showed high titre throughout. Of the 57 cases, 16 (28.07%) were found to be positive for JEV antibodies (7 from paired sera and 9 from single serum). As this hospital is a State referral center for JE, most of the cases with history of acute onset of fever, headache, vomiting, altered sensorium with or without convulsions and other neurological deficits as case of acute encephalitis with strong suspicion of JE are referred to this hospital. Thus, we see a large number of JE cases.

Duration of illness also affects IgM antibody titre. As IgM appears immediately after infection in most cases, it does not present in high titre3. JE infection in its prodromal phase is of very nonspecific type, so it is possible that by the time patient reports and JE is suspected and sample is collected, IgM falls and becomes undetectable by ELISA. As IgG appears later and its concentration increases thereafter3, it is detectable by an appropriate test. Thakare et al* had suggested that MAC-ELISA negative samples should also be tested for JEV specific IgG subclass before ruling out the possibility of JE. So, HI can be used to make a diagnosis of JE either in avery early phase or in late phase of illness.

In the present study, maximum number of JE cases were in the age group less than 12 yr and the number decreased as the age increased. JEV mainly affected paediatric age group. In 1975, Chatterjee et al5 reported that mainly younger age groups were affected by JE. Later in 1982 Mathur et al2 showed that in epidemics of 1978 no age group was spared but more cases occurred in children below 10 yr of age. Outbreaks occurred in 1988 in UP also affected all age groups and maximum incidence was seen in children6.

Males are usually affected more than females. Of the 57 cases, 43 were males and 14 were females. Of the 16 JE positive cases, 10 were males. It may be due to the reason of males sleeping outside the houses with bare body.

Mosquito population increases after rains and there is an increase in the incidence of JE cases7. JE is mainly thought to be a disease of rural area8 but in the present study (36.36%) cases were reported from urban area, 63.63 per cent from rural area.

Most of the cases presented with fever and altered sensorium. In India, Reuben et aP reported the range of case fatality from 10-60 per cent and Kumar et aP have given a range of 20-50 per cent. In our study, case fatality was 12.5 per cent of patients. The low case fatality may be because our study population was small and some of the cases could not be followed up, other reasons could be improved hospital facilities and symptomatic care.

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