Great Pandemic Research Articles

Structure, Receptor Binding, and Antigenicity of Influenza Virus Hemagglutinins from the 1957 H2N2 Pandemic

The hemagglutinin (HA) envelope protein of influenza viruses mediates essential viral functions, including receptor binding and membrane fusion, and is the major viral antigen for antibody neutralization. The 1957 H2N2 subtype (Asian flu) was one of the three great influenza pandemics of the last century and caused 1 million deaths globally from 1957 to 1968. Three crystal structures of 1957 H2 HAs have been determined at 1.60 to 1.75 A resolutions to investigate the structural basis for their antigenicity and evolution from avian to human binding specificity that contributed to its introduction into the human population. These structures, which represent the highest resolutions yet recorded for a complete ectodomain of a glycosylated viral surface antigen, along with the results of glycan microarray binding analysis, suggest that a hydrophobicity switch at residue 226 and elongation of receptor-binding sites were both critical for avian H2 HA to acquire human receptor specificity. H2 influenza viruses continue to circulate in birds and pigs and, therefore, remain a substantial threat for transmission to humans. The H2 HA structure also reveals a highly conserved epitope that could be harnessed in the design of a broader and more universal influenza A virus vaccine.

Fuller Albright

The authors have been involved in the study of mineral metabolism for a good part of our academic careers. As such, we have admired, studied, and benefited from the scientific work and writings of Fuller Albright, whose productive career at Harvard Medical School and the Massachusetts General Hospital spanned almost 30 yr from the late 1920s until 1956. The senior author, Charles Kleeman, was a house officer at Boston City Hospital in 1948 when he first read Fuller Albright's remarkable book Parathyroid Glands and Metabolic Bone Disease (1). This landmark publication summarized Albright's many contributions to mineral metabolism during the previous two decades. Our goal in this historical review is: 1) to describe Albright, the man and his life; 2) review some of his major research accomplishments; and 3) conclude by citing an appreciation of Albright by several of his coworkers and trainees. Fuller Albright was born in Buffalo, New York, on January 12, 1900. His father was a wealthy industrialist and philanthropist. The major art museum in Buffalo is known today as the Albright-Knox Art Gallery. Albright attended the Nichols School in Buffalo, which was founded by his father. He not only excelled academically, but also was captain of the football team. During his childhood, the Albright family made frequent visits to Wilmurt Lake in the Adirondacks, where he became an avid fly fisherman and developed woodsman's skills. During his academic years in Boston, Albright would spend summer vacations at Wilmurt Lake with his family. It was at Wilmurt Lake where he directed that his ashes be scattered after his death. Fuller Albright attended Harvard College, but after only 18 mo, he falsified his age and enlisted in the Army after America's entry into World War I. It was also the time of the great influenza pandemic, which has …

Epidemics of epidemics

Dread: How Fear and Fantasy have Fueled Epidemics from the Black Death to Avian Flu Philip Alcabes Public Affairs US 2009 336 $26.95 9781586486181 As we tremble in anticipation of the predicted second wave of the great swine flu pandemic, Philip Alcabes tells us that can be confident of one thing. Contrary to the apocalyptic hype, history — in the form of the 1918 Spanish Flu pandemic that killed 50 million, perhaps 70 million, people worldwide — will not repeat itself. Although it was written before the emergence of swine flu from Mexico earlier this year, Alcabes' thoughtful historical study of epidemics provides valuable insights into our current predicament. ‘The great calamities’, writes Alcabes, ‘are always, and have always been, unforeseeable and unimaginable until the moment they begin’. He argues persuasively that it is a waste of time and energy to prepare for what we can't foresee and ‘a lie to pretend that we can …

The Fog of Research: Influenza Vaccine Trials during the 1918-19 Pandemic

Bacterial vaccines of various sorts were widely used for both preventive and therapeutic purposes during the great influenza pandemic of 1918-19. Some were derived exclusively from the Pfeiffer's bacillus, the presumed cause of influenza, while others contained one or more other organisms found in the lungs of victims. Although initially most reports of the use of these vaccines claimed that they prevented influenza or pneumonia, the results were inconsistent and sometimes contradictory. During the course of the debates over the efficacy of these vaccines, it became clear that the medical profession had no consensus on what constituted a proper vaccine trial. Even among those who asserted that clinical impression was not enough, there was no agreement on how a trial ought to be conducted. The American Public Health Association, through its Working Program on Influenza, sought to establish standards for the profession. The standards the APHA set in December 1918 guided American vaccine trials for a quarter century.

Bovine and human-derived passive immunization could help slow a future avian influenza pandemic

An epidemic of human transmitted avian influenza could have casualties on a scale seen in the great Spanish influenza pandemic of 1918. This paper proposes that should such occur before effective vaccines and antiviral drugs are available, the outbreak could be significantly slowed by consumption of raw milk produced by herds of pathogen-free lactating cows intranasally inoculated with heat-sterilized sputa pooled from avian influenza patients, supplemented by parenteral serum immune globulin from the same cows. Efficiency of bovine antibody production could be enhanced using cholera toxin subunit b, and milk production could be rapidly accelerated using recombinant bovine somatotropin hormone. In this way, it would be possible to quickly create and distribute large quantities of milk-based and serum-based passive immune globulin active against the strains of avian influenza present in a particular geographic area and gain time for production of human convalescent plasma and other public health measures. This novel approach might also have utility for other serious respiratory infectious diseases, including non-avian influenza, SARS, hantavirus, respiratory syncytial virus, antibiotic-resistant Streptococcus pneumoniae and pneumonia-causing Staphylococcus aureus.

Disease and destiny–mystery and mastery

When early people made their appearance, zoonotic infectious diseases were already waiting, but epidemic diseases did not appear in human history until people began to live in large numbers under conditions of close contact, mainly during the last 10,000 years. Disease has decimated urban populations, conquered armies, and disrupted society. The focus here is on (1) the plague of Athens and the Black Death; (2) smallpox, influenza, and rabies; (3) avian influenza prion diseases, and foot & mouth disease; and (4) emerging and re-emerging diseases. All have veterinary public health associations. In Athens, Greece, in 430 BC, when the Spartans ravaged the countryside, hordes crowded into Athens so that orderly movements, space in which to live, and adequate supplies of food became impossible. Crowding of any population fosters disease transmission; chaos and disorder enhance it all the more. Out of northern Egypt came a terrible plague from across the Mediterranean Sea. The identity of the plague of Athens remains unsure, but the well-considered conclusion is Rift Valley Fever, a mosquito borne, viral zoonosis. The Black Death, also called the Plague, raged in Asia for centuries. In 1347, the Black Death was brought by a ship out of Asia to Sicily. The scenes of devastation were repeated throughout Europe, with 90% or more of the people dying in city after city. Influenza, too, has been a cause of periodic human epidemics, but the great pandemic of influenza occurred in the last months of World War I. In the years of highest occurrence, more than half the world's population became clinically infected. If veterinary public health had been born earlier, it could have led to elucidating the epidemiology of influenza and the plagues of Athens, Europe, and Asia. In turn, smallpox had also caused continual tragedy. In 1796, Edward Jenner began to harvest pustules of cowpox from children or infected cows and inject them into susceptible children. In 1980, the World Health Organization declared that smallpox had been eliminated from the world. Rabies, though, still strikes terror. A number of animal diseases, broadly termed emerging and re-emerging diseases, need surveillance because they have the potential to impact human health. From late in 2003 to 2007, the highly pathogenic H5N1 influenza virus in poultry infected at least 121 people and caused 62 deaths in four countries. The prion diseases, too, all have very high numbers in concentrated contacts. To control these diseases, veterinary public health is essential, with diagnosis, epidemiological surveillance, clinical manifestations, and prevention as primary measures.

Sound of Music Echoes Through Brain Regions

Back to table of contents Previous article Next article Association NewsFull AccessSound of Music Echoes Through Brain RegionsMark MoranMark MoranSearch for more papers by this authorPublished Online:6 Jun 2008https://doi.org/10.1176/pn.43.11.0004Oliver Sacks, M.D.: “One could say that music never sleeps” in a person's mind.Credit: David HathcoxMusic and the mind was the subject of an address by neurologist and famed author Oliver Sacks at the Convocation of Fellows at APA's 2008 annual meeting in Washington, D.C., last month.Using the stories of curious and uncanny psychological phenomena for which he has become known, the author of the 2007 book Musicophilia: Tales of Music and the Brain told psychiatrists and their guests that music is heard in regions of the brain that regulate both motor movements and emotion.For that reason, music is uniquely capable of influencing behavior. He noted, for instance, that during the processional when he and APA fellows filed into the convocation hall earlier that evening, he felt himself beginning to walk in time to the music.“Music is at once sensory, emotional, aesthetic, and motor,” Sacks said. He said he believes music can be usefully incorporated into therapy for neurological and psychiatric conditions, including the most severe disorders.“Most of us also experience music in the mind, musical imagery which tends to be involuntary,” Sacks said. This is a feature of the brain that he said “alleviates boredom and fatigue and buoys the spirit.”And music is also heard in dreams. “So one could say that music never sleeps,” he said. In fact, he suggested that psychiatrists ask their patients not only about their dreams but also about the music they hear in their minds. Like dreams, such music can reveal meaningful material.He also described stories gathered from his own clinical practice, and from stories and anecdotes sent to him by readers, of individuals who experienced musical hallucinations—who believed they heard music when none was playing. For instance, he described a man who became fixated on the song“ Love and Marriage,” made famous initially by Frank Sinatra and later as the theme song of the popular television series “Married... With Children.”“He got trapped inside the tempo of the song,” Sacks said.“ After incessant repetition, the song lost all its charm and musicality and began to interfere with his schoolwork.”Another woman he described was visiting her sister over a holiday when she began to hear the melody of “Amazing Grace” so convincingly that she believed that it must have been playing in a nearby church. Later, the woman wrote to Sacks about the experience, telling him, “I looked down and realized the music couldn't possibly be coming from anywhere but inside my head.”She sent Sacks a “playlist” that included the “Battle Hymn of the Republic,” Beethoven's “Ode to Joy,” the drinking song from “La Traviata,” and “A Tisket, a Tasket.”“And one night,” he quoted the woman as telling him, “I heard a splendidly solemn version of 'Old MacDonald Had a Farm'—followed by thunderous applause.”“She was perfectly sane,” Sacks said. “Many people experience musical hallucinations, and I am sure it is underreported. About 80 percent have severe deafness. Among older people particularly, [deafness] conduces to musical hallucinations.“It is as if the auditory cortex isn't getting its crucial nourishment,” Sacks said. “So it delves down into memory and regurgitates music from childhood or earlier in life, in the same way that people with visual impairments can have visual hallucinations.“People are afraid to mention these for fear of being perceived as crazy. One subject talked about his intracranial jukebox.”According to Sacks's official Web site at<www.oliversacks.com>, the British-born physician and author began working as a consulting neurologist for Beth Abraham Hospital in the Bronx, a chronic-care hospital where he encountered patients who had spent decades in strange, frozen states, like human statues, unable to move.Sacks recognized these patients as survivors of the great pandemic of sleeping sickness that had swept the world from 1916 to 1927. He treated them with a then-experimental drug, levodopa, which enabled them to come back to life. They became the subjects of his book Awakenings, which later inspired a play by Harold Pinter (“A Kind of Alaska”) and the Oscar-nominated feature film (“Awakenings”) with Robin Williams and Robert De Niro.He has since become known for his collections of case histories describing rare and remarkable neurological experiences and phenomena. In The Man Who Mistook His Wife for a Hat and An Anthropologist on Mars, he describes patients struggling to live with conditions such as Tourette's syndrome, autism, parkinsonism, musical hallucinations, epilepsy, phantom limb syndrome, schizophrenia, retardation, and Alzheimer's disease.In July 2007 he was appointed a professor of clinical neurology and clinical psychiatry at Columbia University Medical Center, and he was designated Columbia University's first Columbia Artist. ▪ ISSUES NewArchived

Learning from the past to prepare for the future: Modeling the impact of hypothetical interventions during the great influenza pandemic of 1918

Learning from the past to prepare for the future: Modeling the impact of hypothetical interventions during the great influenza pandemic of 1918

An Alternative View: Pandemic ‘Flu and Intensive Care – an Ethical Minefield

Images of the great influenza pandemics of the past are replete with crowded hospitals the size of aircraft hangars, along with armed guards protecting healthcare workers (HCWs). It is hardly something of which the current generation have any direct memory. These images are more like fiction than recent history, but the vision of a UK pandemic in our near future is not fantasy. Scenarios of more than a million sick, infected patients with mortalities varying from 25-50% have been produced, and it is not surprising that the WHO states on its website that “economic and social disruption will be severe and that large numbers of deaths will occur.” The arrival of such a pandemic will produce ethical challenges to the way that health care is delivered and managed in the UK, of the sort not seen for decades. One does not have to envision an apocalyptic event to realise how problematical managing a pandemic would be. This government has trumpeted, for good reason, a health service that is designed to respond to individual needs and demands, and we enjoy a society that has become accustomed to an individually focused healthcare system. Even conservative modelling suggests that during a pandemic there would be 14 million infected patients in the UK.1 A proportion of these will require hospitalisation and a proportion of those hospitalised will compete for scarce intensive care beds. If a pandemic occurs, the fact that ICU beds will be scarce is certain. 2

James Joyce and Germ Theory: The Skeleton at the Feast

In Shakespeare and Company, Sylvia Beach recollects that Joyce was afraid of thunderstorms, heights, the sea, dogs, and infection.' A healthy fear of germs and contagion would not be surprising among the members of the Irish population born in the nineteenth century who were lucky enough to survive. At least 775,000 people died in Ireland during the famine years (1846-1851), mostly from contagious disease, especially cholera.2 There were four influenza epidemics from 1890-1894 that spread from Europe to England, Scotland, and Ireland, and during the week ending on 23 January 1892 alone, medical historians estimate 1,858 Londoners died of influenza and the probable complications of bronchitis and pneumonia.3 Even in the absence of acute epidemics, tuberculosis routinely ended the lives of between one in ten and one in seven Europeans; infant mortality and childhood deaths from all causes were worse in Dublin than in Calcutta, and five of Joyce's siblings did not survive into adulthood.4 To complicate matters, the incidence of infectious disease was accompanied by a perceived, steady rise in lunacy that was alarming the British and Irish populations. A generation later, while Joyce was writing Ulysses, the great influenza pandemic of 1918-1920 dwarfed these epidemiological figures and killed fifty to one hundred million worldwide.5 The fear of infection in the early twentieth century, especially in someone who was attuned to medical issues, would hardly have been phobic. In Joyce's younger days, germ theory was still the subject of serious debate, both among scientists and members of the medical profession. For much of the nineteenth century, disease was thought to be miasmic, that is, caused by a poison that lurks in the environment: in the water, air, or soil. The theory of contagious disease transmission devised by Louis Pasteur, Robert Koch, and other bacteriologists was not monolithically accepted, and even among proponents of germ theory, there was an active discussion about the agents of infection. It was debated whether bacteria caused diseases or whether diseases

The US pandemic influenza implementation plan at six months

There has been great concern recently about pandemic influenza. The US government developed a National Strategy for Pandemic Influenza in November 2005, followed by an implementation plan in May 2006. A sixmonth progress report was published in late December. The current strategies are intended to improve preparedness and response for the next influenza pandemic. In comparison with the optimistic neglect that often characterized past planning for pandemic influenza, there has been considerable progress on a number of fronts in the past year. Despite this progress, major gaps remain. These include the coordination, encouragement and funding of international surveillance and cooperation; the need for new and more agile vaccine technologies; limitations in the use and distribution of antiviral agents; and communication with, and resources for, local responders and the public. One question is why, despite an estimated 36,000 seasonal influenza deaths annually in the United States alone, and a much greater number during pandemics, relatively little new basic research has been done for decades. This emphasizes both the need for and the difficulty of sustaining pandemic preparedness. There is good reason to be concerned about a future influenza pandemic. There were three in the twentieth century, in 1918–1919, 1957 and 1968, and most virologists believe that pandemics are inevitable1. The greatest influenza pandemic, in 1918–1919, was also the worst natural disaster in recorded history, with an estimate of over 50 million deaths worldwide2–4. Concern about the state of pandemic preparedness and response has been increasing over the last decade. In 1999, when the World Health Organization (WHO) produced pandemic planning recommendations, only Canada and the UK already had plans. By 2007, 29 countries had submitted plans (available at http://www.who.int/csr/disease/avian_ influenza/links/en/index.html) to WHO. Next year will mark the 90th anniversary of the great pandemic of 1918, making it especially timely to take stock of our readiness for the next pandemic. On 1 November 2005, the President of the United States declared that “nature has presented us with a daunting challenge: the possibility of an influenza pandemic,” and announced the government’s National Strategy for Pandemic Influenza (http://www. pandemicflu.gov, under Federal Planning). This strategy is intended to address the next influenza pandemic, whichever influenza virus is the cause. Although we do not know whether the H5N1 avian influenza strain will ever develop the ability to spread readily from person to person and thus become pandemic, this virus has recently been getting close scrutiny. It has already caused serious human illness and deaths, primarily although not exclusively through close contact with infected poultry. There have also been tremendous economic losses for poultry farmers.

Pandemic influenza: Studying the lessons of history

Next year will mark the 90th anniversary of the great influenza pandemic of 1918, an event widely considered to be one of the greatest natural disasters in human history. Historians estimate that ≥50 million people died worldwide, including >450,000 documented deaths in the United States alone (1). Since then, the 20th century witnessed two more influenza pandemics, although fortunately none comparable in ferocity to the 1918 pandemic (2). Pandemics—epidemics so large that virtually the entire world is affected—have occurred several times in each of the last several centuries. Most virologists therefore believe that it is inevitable that we will experience at least one pandemic in this century, and very likely more. However, if a pandemic were to strike in the near future, it is likely that vaccine would not be available for at least 4–6 months (3). Antivirals, if effective against the pandemic strain, would probably also be in short supply. Few of these measures can be applied at pandemic scale, in which half the population of the world would likely be infected over the course of a year or more. We would be left with other measures, now termed “nonpharmaceutical interventions,” to stave off the worst effects of a pandemic until a vaccine could be produced and widely administered (4, 5). Because many of these interventions, such as closing schools or shutting down mass transit, could be very disruptive to society, it is important to use effective measures in a rational way. But which measures are most effective, and how should they be applied? Do any nonpharmaceutical interventions actually help? Until now, there has been very little systematic examination of these questions. However, different U.S. cities showed marked differences in influenza attack rates and mortality in 1918. Some cities, St. Louis for example, appeared to have weathered the …

Training the nation’s responders for pandemic influenza: A Department of Homeland Security planning and preparedness initiative

Communities all over the world are preparing for the next disaster. Lately, the World Health Organization has focused its attention on H5N1, a subtype of the influenza virus. H5N1, which most Americans recognize as “bird flu,” has caused massive losses in poultry production, as well as some human fatalities. Public officials have been warned that H5N1 may mutate into a strain that is not only highly pathogenic but also readily transmissible between humans. Should this occur, we might find ourselves on the verge of the next great pandemic. Because of this, community leaders, public health officials, and responders at planning and management levels face one of their most challenging problems: planning and preparing for pandemic influenza. Recently, an initiative at the Center for Domestic Preparedness was undertaken to assemble a training program for community leaders and senior responders that will address the current threat of a pandemic, outline an appropriate response to the problem, and exercise small planning teams using a tabletop model.

The Black Death and AIDS: CCR5- 32 in genetics and history

Black Death and AIDS are global pandemics that have captured the popular imagination, both attracting extravagant hypotheses to account for their origins and geographical distributions. Medical scientists have recently attempted to connect these two great pandemics. Some argue that the Black Death of 1346-52 was responsible for a genetic shift that conferred a degree of resistance to HIV 1 infection, that this shift was almost unique to European descendents, and that it mirrors the intensity of Black Death mortality within Europe. Such a hypothesis is not supported by the historical evidence: the Black Death did not strike Europe alone but spread from the east, devastating regions such as China, North Africa, and the Middle East as much or even more than Europe. Further, in Europe its levels of mortality do not correspond with the geographic distribution of the proportion of descendents with this CCR5 gene. If anything, the gradient of Black Death mortality sloped in the opposite direction from that of present-day genotypes: the heaviest casualties were in the Mediterranean, the very regions whose descendents account for the lowest incidences of the HIV-1 resistant allele. We argue that closer collaboration between historians and scientists is needed to understand the selective pressures on genetic mutation, and the possible triggers for changes in genetic spatial frequencies over the past millennia. This requires care and respect for each other's methods of evaluating data.

Transmission dynamics of the great influenza pandemic of 1918 in Geneva, Switzerland: Assessing the effects of hypothetical interventions

Recurrent outbreaks of the avian H5N1 influenza virus in Asia represent a constant global pandemic threat. We characterize and evaluate hypothetical public health measures during the 1918 influenza pandemic in the Canton of Geneva, Switzerland. The transmission rate, the recovery rate, the diagnostic rate, the relative infectiousness of asymptomatic cases, and the proportion of clinical cases are estimated through least-squares fitting of the model to epidemic curve data of the cumulative number of hospital notifications. The latent period and the case fatality proportion are taken from published literature. We determine the variance and identifiability of model parameters via a simulation study. Our epidemic model agrees well with the observed epidemic data. We estimate the basic reproductive number for the spring wave R 1 ^ = 1.49 ( 95 % CI: 1.45 – 1.53 ) and the reproductive number for the fall wave R 2 ^ = 3.75 ( 95 % CI: 3.57 – 3.93 ). In addition, we estimate the clinical reporting for these two waves to be 59.7 % ( 95 % CI: 55.7 – 63.7 ) and 83 % ( 95 % CI: 79 – 87 ). We surmise that the lower reporting in the first wave can be explained by a lack of initial awareness of the epidemic and the relative higher severity of the symptoms experienced during the fall wave. We found that effective isolation measures in hospital clinics at best would only ensure control with probability 0.87 while reducing the transmission rate by > 76.5 % guarantees stopping an epidemic.

HIV: Dark and Light, Then and Now

A ‘return’ of epidemics & pandemics? By approximately the mid-1970s much of the medical science community became confident that serious epidemics were no longer significant problems for developed nations. There was also a strong prevailing view that retroviruses did not infect humans. Such sentiments led to the closures of microbiology departments in some medical schools and the termination of the US Virus Cancer Program. Yet, within a span of a few years human retroviruses were discovered. Some were shown to cause certain types of leukemia as well as neurologic disease (human T-cell leukemia virus [HTLV]-1); and several old epidemics re-emerged while new epidemics emerged including perhaps the greatest pandemic in medical history, AIDS, caused by the HIV retrovirus.

Dangerous Illusions: Cautionary Tales In The History Of Medicine

The recent deaths from avian influenza in Vietnam, Cambodia, and Thailand have generated much concern that avian flu could be the world’s next great pandemic. As of this writing, forty-eight people have died and tens of millions of birds have been slaughtered. Microbiologists fear that if the current strain, which has been passed from bird to bird and from bird to human, were to evolve to allow human to human passage, it could quickly kill millions. What does this mean for our faith in modern medicine? Gerald Grob’s expansive history, spanning the centuries from colonial America to the present, seems ever more relevant as we contemplate this latest epidemiological threat. Grob shatters the comfortable assumption that the future of medicine is one of unlimited progress. Documenting the experience of disease in America, from smallpox to AIDS, he explores the many variables that have shaped epidemics and the role of medicine in containing them. After presenting extensive and detailed evidence, he argues that increased natural immunity, reduced pathogen virulence, improvements in nutrition, and broad public health policies have been much more important influences on declining mortality from infectious diseases than have medical discoveries or treatments. The continuing belief that medicine has played a larger role, and that further progress is inevitable and infinite, provides a false sense of security and may have had a deleterious effect on the design of research studies, funding allocations, and environmental and occupational health policy. As Grob concludes, “the faith that disease can be completely conquered is at best a harmless and at worst a dangerous utopian illusion” (p. 274). Beginning with the early colonization of America, Grob focuses on the major threats to health in each era for different groups of the population. Class, race, and gender are not central categories of his analysis; instead he concentrates attention on the biological “realities” of specific diseases and the population factors that nurture their spread. In meticulous detail, using a vast array of examples from across the country, he documents the terrible toll of contagious diseases on America’s indigenous Indian populations and the early colonists. He clearly establishes the role of previous exposure in creating immunity, as well as the broad array of variables that influence the impact of epidemics—so that the same disease has had different effects in various geographic locations and social environments and on older or younger populations. Grob then turns to the major epidemiological shift of the late nineteenth and early twentieth centuries, in which chronic illnesses overtook infectious diseases as the strongest driver of the country’s mortality rates. He explores various explanations for the declining significance of infectious diseases and draws particular attention to the epidemics of ill

Avian influenza: perfect storm now gathering?

Avian influenza: perfect storm now gathering?

Would you volunteer to be quarantined and infected with influenza virus?

During the great pandemic of 1918, when the precise nature of the causative microbe of the Spanish influenza had not been established, a group of American scientists asked for young volunteers from...

Blocking HIV-1 Vif Restores a Natural Mechanism of Intracellular Antiviral Defense

AIDS has become the greatest pandemic in the human history counting approximately 40 millions people worldwide. To purge HIV-1 infection, new therapeutic approaches need to be searched in alternative and/or in addition to the current pharmacological ones. Recently, several independent laboratories have unveiled a non-immune intracellular anti-HIV-1 defense strategy based on the cytidine deaminase APOBEC3G, which restricts HIV-1 production by directly mutating the proviral DNA in infected cells. To counteract this defense pathway, HIV-1 has developed an evasion strategy by acquiring the accessory protein Vif, which blocks the action of APOBEC3G by inducing its proteasome-mediated degradation.