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How do viruses get into cells? Their infection tactics determine whether they can jump species or set off a pandemic

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How do viruses get into cells? Their infection tactics determine whether they can jump species or set off a pandemic

Surface proteins on a virus enable it to attach to and get inside a cell to start replicating.
koto_feja/E+ via Getty Images

Peter Kasson, University of Virginia

COVID-19, flu, mpox, noroviral diarrhea: How do the viruses that cause these diseases actually infect you?

Viruses cannot replicate on their own, so they must infect cells in your body to make more copies of themselves. The life cycle of a virus can thus be roughly described as: get inside a cell, make more virus, get out, repeat.

Getting inside a cell, or viral entry, is the part of the cycle that most vaccines target, as well as a key barrier for viruses jumping from one species to another. My lab and many others study this process to better anticipate and combat emerging viruses.

How viruses enter cells

Different viruses travel into the body in various ways – via airborne droplets, on food, through contact with mucous membranes or through injection. They typically first infect host cells near their site of entry – the cells lining the respiratory tract for most airborne viruses – then either remain there or spread throughout the body.

Viruses recognize specific proteins or sugars on host cells and stick to them. Each virus gets only one shot at putting its genome inside a cell – if their entry machinery misfires, they risk becoming inactivated. So they use several mechanisms to prevent triggering entry prematurely.

After the virus binds to the cell, specific molecules on the cell’s surface or within the cell’s recycling machinery activate viral coat proteins for entry. An example is the SARS-CoV-2 spike that COVID-19 vaccines target. These proteins need to modify the cell membrane to allow the viral genome to get through without killing the cell in the process. Different viruses use different tricks for this, but most work like cellular secretion – how cells release materials into their environment – in reverse. Specialized viral proteins help merge the membranes of the virus and the cell together and release the viral core into the interior of the cell.

This animation depicts HIV fusing its membrane with a cell in order to release its contents inside.

At this point, the viral genome can enter the cell and start replicating. Some viruses use only the cell’s machinery to replicate, while others carry along portions of their own replication machinery and borrow some parts from the cell. After replicating their genomes, viruses assemble the components required to make new viruses.

Two central questions scientists are studying about viral entry are how your body’s defenses can disrupt it and what determines whether a virus from other species can infect people.

Immune defenses against viruses

Your body has a multilayered defense system against viral threats. But the part of your immune system called the antibody response is generally thought to be most effective at sterilizing immunity – preventing an infection from taking hold in the first place as opposed to just limiting its scope and severity.

For many viruses, antibodies target the part of the virus that binds to cells. This is the case not just for current COVID-19 vaccines but also the majority of immunity against influenza, whether from vaccines or from prior infection.

However, some antibodies target the entry machinery instead: Rather than preventing the virus from sticking, they prevent the virus from working altogether. Such antibodies are often harder for the viruses to escape from but are difficult to reproduce with vaccines. For that reason, developing antibodies that inhibit cell entry has the been the goal of many next-generation vaccine efforts.

Diagram of the mechanisms of four classes of HIV antivirals
This diagram shows how four different classes of antiviral drugs inhibit HIV. One stops viruses from entering cells, and three inhibit different viral enzymes.
Thomas Splettstoesser/Wikimedia Commons, CC BY-SA

Species-hopping and pandemics

The other key question researchers are asking about viral entry is how to tell when a virus from another species poses a threat to people. This is particularly important because many viruses are first identified in animals such as bats, birds and pigs before they spread to humans, but it’s unclear which ones may cause a pandemic.

The part of viruses that stick to human cells varies the most across species, while the part that gets the virus into cells tends to stay mostly the same. Many researchers have thought that viruses changing in ways that bind better to human cells, like influenza viruses that bind to cells in the nose and throat, are some of the most important warning signs for pandemic risk.

However, coronaviruses – the family of viruses containing SARS-CoV-2 – are prompting re-examination of that idea. This is because several animal coronaviruses can actually bind to human cells, but only a few seem to be able to transmit well between people.

Only time will tell whether researchers need to broaden their pandemic prevention horizons or if their current prioritization of risky viruses is correct. The one grim reality of pandemic research, like earthquake research, is that there will always be another one – we just don’t know when or where, and we want to be ready.The Conversation

Peter Kasson, Professor of Molecular Physiology and Biomedical Engineering, University of Virginia

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Medical research depends on government money – even a day’s delay in the intricate funding process throws science off-kilter

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theconversation.com – Aliasger K. Salem, Associate Vice President for Research and Professor of Pharmaceutical Sciences, University of Iowa – 2025-01-28 07:51:00

Medical research depends on government money – even a day’s delay in the intricate funding process throws science off-kilter

Of the tens of thousands of grant applications submitted to the National Institutes of Health, only around 1 in 5 is funded.
Sean Gladwell/Moment via Getty Images

Aliasger K. Salem, University of Iowa

In the early days of the second Trump administration, a directive to pause all public communication from the Department of Health and Human Services created uncertainty and anxiety among biomedical researchers in the U.S. This directive halted key operations of numerous federal agencies like the National Institutes of Health, including those critical to advancing science and medicine.

These operations included a hiring freeze, travel bans and a pause on publishing regulations, guidance documents and other communications. The directive also suspended the grant review panels that determine which research projects receive funding.

As a result of these disruptions, NIH staff has reported being unable to meet with study participants or recruit patients into clinical trials, delays submitting research findings to science journals, and rescinded job offers.

Shorter communication freezes in the first few days of a new administration aren’t uncommon. But the consequences of a freeze lasting weeks or potentially longer underscore the critical role the federal government plays in supporting biomedical research. It also brings the intricate processes through which federal research grants are evaluated and awarded into the spotlight.

I am a member of a federal research grant review panel, as well as a scientist whose own projects have undergone this review process. My experience with the NIH has shown me that these panels come to a decision on the best science to fund through rigorous review and careful vetting.

How NIH study sections work

At the heart of the NIH’s mission to advance biomedical research is a careful and transparent peer review process. Key to this process are study sections – panels of scientists and subject matter experts tasked with evaluating grant applications for scientific and technical merit. Study sections are overseen by the Center for Scientific Review, the NIH’s portal for all incoming grant proposals.

A typical study section consists of dozens of reviewers selected based on their expertise in relevant fields and with careful screening for any conflicts of interest. These scientists are a mix of permanent members and temporary participants.

I have had the privilege of serving as a permanent chartered member of an NIH study section for several years. This role requires a commitment of four to six years and provides an in-depth understanding of the peer review process. Despite media reports and social media posts indicating that many other panels have been canceled, a section meeting I have scheduled in February 2025 is currently proceeding as planned.

Person wearing glasses reviewing a stack of papers, surrounded by other stacks of papers on a desk
Evaluating projects for their scientific merit and potential impact is an involved process.
Center for Scientific Review

Reviewers analyze applications using key criteria, including the significance and innovation of the research, the qualifications and training of the investigators, the feasibility and rigor of the study design, and the environment the work will be conducted in. Each criterion is scored and combined into an overall impact score. Applications with the highest scores are sent to the next stage, where reviewers meet to discuss and assign final rankings.

Because no system is perfect, the NIH is constantly reevaluating its review process for potential improvements. For example, in a change that was proposed in 2024, new submissions from Jan. 25, 2025, onward will be reviewed using an updated scoring system that does not rate the investigator and environment but takes these criteria into account in the overall impact score. This change improves the process by increasing the focus of the review on the quality and impact of the science.

From review to award

Following peer review, applications are passed to the NIH’s funding institutes and centers, such as the National Institute of Allergy and Infectious Diseases or the National Cancer Institute, where program officials assess the applications’ alignment with the priorities and budgets of institutes’ relevant research programs.

A second tier of review is conducted by advisory councils composed of scientists, clinicians and public representatives. In my experience, study section scores and comments typically carry the greatest weight. Public health needs, policy directives and ensuring that one type of research is not overrepresented relative to other areas are also considered in funding decisions. These factors can change with shifts in administrative priorities.

Grant awards are typically announced several months after the review process, although administrative freezes or budgetary uncertainties can extend this timeline. Last year, approximately US$40 billion was awarded for biomedical research, largely through almost 50,000 competitive grants to more than 300,000 researchers at over 2,500 universities, medical schools and other research institutions across the U.S.

Getting federal funding for research is a highly competitive process. On average, only 1 in 5 grant applications is funded.

Scientist looking into microscope, surrounded by other lab equipment
Medical research often follows a strict timeline.
gorodenkoff/iStock via Getty Images Plus

Consequences of an administrative freeze

The Trump administration’s initial freeze paused some of the steps in the federal research grant review process. Some study section meetings have been postponed indefinitely, and program officials faced delays in processing applications. Some research groups relying on NIH funding for ongoing projects can face cash flow challenges, potentially resulting in a need to scale back research activities or temporarily reassign staff.

Because my own study section meeting is still scheduled to take place in February, I believe these pauses are temporary. This is consistent with a recent follow-up memo from acting HHS Secretary Dorothy Fink, stating that the directive would be in effect through Feb. 1.

Importantly, the pause underscores the fragility of the research funding pipeline and the cascading effects of administrative uncertainty. Early-career scientists who often rely on timely grant awards to establish their labs are particularly vulnerable, heightening concerns about workforce sustainability in biomedical research.

As the NIH and research community navigate these pauses, this chapter serves as a reminder of the critical importance of stable and predictable funding systems. Biomedical research in the U.S. has historically maintained bipartisan support. Protecting the NIH’s mission of advancing human health from political or administrative turbulence is critical to ensure that the pursuit of scientific innovation and public health remains uncompromised.The Conversation

Aliasger K. Salem, Associate Vice President for Research and Professor of Pharmaceutical Sciences, University of Iowa

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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In asking Trump to show mercy, Bishop Budde continues a long tradition of Christian leaders ‘speaking truth to power’

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theconversation.com – Joanne M. Pierce, Professor Emerita of Religious Studies, College of the Holy Cross – 2025-01-28 07:50:00

In asking Trump to show mercy, Bishop Budde continues a long tradition of Christian leaders ‘speaking truth to power’

Bishop Mariann Budde leads the national prayer service attended by President Donald Trump at the National Cathedral in Washington on Jan. 21, 2025.
AP Photo/Evan Vucci

Joanne M. Pierce, College of the Holy Cross

Episcopal Bishop Mariann Edgar Budde’s sermon on Jan. 21, 2025, in which she appealed to President Donald Trump to have mercy toward groups frightened by his position on immigrants and LGBTQ+ people – especially children – drew reactions from both sides of the aisle.

In a post on his social networking site, Truth Social, Trump called her comments “nasty in tone” and remarked that she “brought her church into the World of politics in a very ungracious way.”

“She and her church owe the public an apology!,” he posted. Several conservatives criticized her sermon, while many progressives saw her as “speaking truth to power.”

As a specialist in medieval Christianity, I was not surprised by the bishop’s words, as I know that Christian history is full of examples of people who have spoken out, unafraid to risk official censure, or even death.

Early voices

Even in the early centuries of Christianity, followers of Jesus Christ’s teachings could be outspoken toward political leaders.

For example, in the first-century Gospels, John the Baptist, a contemporary of Jesus, confronts the ruler of Galilee, Herod Antipas, for marrying his brother’s wife – a practice forbidden in the Hebrew scriptures. For that, John the Baptist was ultimately beheaded.

In a prayer later called the Magnificat, Mary, the mother of Jesus, praises the glory and power of God who casts down the mighty and raises the lowly. In recent interpretations, these words have been understood as a call for those in authority to act more justly.

In the late fourth century – a time when Christianity had been made the official religion of the Roman Empire – a respected civil official named Ambrose became bishop of the imperial city of Milan in northern Italy. He became well known for his preaching and theological treatises.

However, after imperial troops massacred innocent civilians in the Greek city of Thessaloniki, Ambrose reproached Emperor Theodosius and refused to admit him to church for worship until he did public penance for their deaths.

Ambrose’s writings on scripture and heresy, as well as his hymns, had a profound influence on Western Christian theology; since his death, he has been venerated as a saint.

In the early sixth century, the Christian Roman senator and philosopher Boethius served as an official in the Roman court of the Germanic king of Italy, Theodoric. A respected figure for his learning and personal integrity, Boethius was imprisoned on false charges after defending others from accusations by corrupt court officials acting out of greed or ambition.

During his time in prison, he wrote a philosophical volume about the nature of what is true good – “On the Consolation of Philosophy” – that is studied even today. Boethius, who was executed in 524, is venerated as a saint and martyr in parts of Italy.

Thomas Becket and St. Catherine

One of the most famous examples of a medieval bishop speaking truth to power is that of Thomas Becket, former chancellor – that is, senior minister – of England in the 12th century. On becoming archbishop of Canterbury, Becket resigned his secular office and opposed the efforts of King Henry II to bring the church under royal control.

A painting depicts three men: one inserting a sword into the man in the middle, while the third, standing to the side, appears to strike with his sword.
A stained glass window at the Canterbury Cathedral in England depicting the murder of Thomas Becket, archbishop of Canterbury.
Dukas/Universal Images Group via Getty Images

After living in exile in France for a time, Becket returned to England and was assassinated by some of Henry’s knights. The king later did public penance for this at Becket’s tomb in Canterbury. Soon after, Becket was canonized a saint.

Another influential saint was the 14th-century Italian mystic and writer Catherine of Siena. Because of the increasing power of the kings of France, the popes had moved their residence and offices from Rome to Avignon, on the French border. They remained there for most of the century, even though this Avignon papacy increased tensions in western Europee.

Many Christian clerics and secular rulers in western Europe believed that the popes needed to return to Rome, to distance papal authority from French influence. Catherine herself even traveled to Avignon and stayed there for months, writing letters urging Pope Gregory XI to return to Rome and restore peace to Italy and the church – a goal the pope finally fulfilled in 1377.

Leaders speak up across denominations

The Reformation era of the 16th and early 17th centuries led to the splitting of Western Christianity into several different denominations. However, many Christian leaders across denominations continued to raise their voices for justice.

One important and ongoing voice is that of the Religious Society of Friends, or Quakers. Early leaders, like Margaret Fell and George Fox, wrote letters to King Charles II of England in the mid-17th century, defending their beliefs, including pacifism, in the face of persecution.

In the 18th century, based on their belief in the equality of all human beings, Quaker leaders spoke in favor of the abolition of slavery in both the United Kingdom and the United States.

In fact, it was Bayard Rustin, a Black Quaker, who coined the phrase “to speak truth to power” in the mid-20th century. He adhered to the Quaker commitment to nonviolence in social activism and was active for decades in the American Civil Rights Movement. During the Montgomery bus boycott in the mid-1950s, he met and began working with Martin Luther King Jr., who was an ordained Baptist minister.

In Germany, leaders from various Christian denominations have also united to speak truth to power. During the rise of the Nazis in the 1930s, several pastors and theologians joined forces to resist the influence of Nazi doctrine over German Protestant churches.

Their statement, the Barmen Declaration, emphasized that Christians were answerable to God, not the state. These leaders – the Confessing Church – continued to resist Nazi attempts to create a German Church.

Desmond Tutu and other leaders

A black-and-white photo shows a grey-haired, spectacled man in a suit and tie, speaking and gesturing with his hands.
Bishop Desmond Tutu opposed the racial policies of the South African government.
AP Photo/Jim Abrams

Christians on other continents, too, continued this vocal tradition. Óscar Romero, the Roman Catholic archbishop of San Salvador, preached radio sermons criticizing the government and army for violence and oppression of the poor in El Salvador during a national civil war. As a result, he was assassinated while celebrating Mass in 1980. Romero was canonized a saint by Pope Francis in 2018.

In South Africa, the Anglican bishop Desmond Tutu, archbishop of Cape Town, spent much of his active ministry condemning the violence of apartheid in his native country. After the end of the apartheid regime, Tutu also served as chair of the Truth and Reconciliation Commission, which was established to investigate acts of violence committed both by government forces and violent activists. Before his death in 2021, Tutu continued to speak out against other international acts of oppression. He won the Nobel Peace Prize in 1984.

For some, Bishop Budde’s words might seem radical, rude, inappropriate or offensive. But she did not speak in isolation; she is surrounded by a cloud of witnesses in the Christian tradition of speaking truth to power.The Conversation

Joanne M. Pierce, Professor Emerita of Religious Studies, College of the Holy Cross

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St. Thomas Aquinas’ skull just went on tour − here’s what the medieval saint himself would have said about its veneration

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theconversation.com – Therese Cory, Associate Professor of Thomistic Studies, University of Notre Dame – 2025-01-28 07:50:00

St. Thomas Aquinas’ skull just went on tour − here’s what the medieval saint himself would have said about its veneration

The skull of St. Thomas Aquinas during a stop at St. Patrick Church in Columbus, Ohio, in December 2024.
Nheyob/Wikimedia Commons

Therese Cory, University of Notre Dame

Once, on a road trip in Greece, I stopped with my husband and dad at a centuries-old Orthodox monastery to view its famous frescoes. We were in luck, the porter said: It was a feast day. The relics of the monastery’s saintly founder were on view for public veneration.

As a Catholic and a medievalist, I can never resist meeting a new saint. The relic, it turned out, was the saint’s hand, though without any special ornament or reliquary, the ornate containers in which relics are often displayed. Nothing but one plain, severed hand in a glass box, its fingers partly contorted, and its discolored skin shriveled onto the bones.

We gathered around the shrine, silently, to pray. Then my dad, whose piety sometimes runs up against his penchant for dramatic storytelling, leaned over and whispered, “What if at the hotel, in the middle of the night, I hear a scratching sound, and then The Claw …” His own hand started crawling dramatically up his shirt and then flew to his throat.

“Dad!” I hissed furiously, with a horrified glance at the monks praying nearby.

Relics can admittedly feel a bit morbid – and yet, so holy. What exactly is their appeal?

To me, it’s the physical closeness, especially with parts of a saint’s own body – what the Catholic Church calls “first class” relics, which can be as small as a chip of bone. There are also objects the saint used during life: “second class” relics, such as the gloves worn by the Italian mystic Padre Pio.

The veneration of relics of saints was already well established in the early church. But controversies go back hundreds of years. During the Protestant Reformation, for example, reformers decried the shameless use of relics to drive donations and the proliferation of faux relics. Today, the idea of intentionally dismembering and displaying human body parts can seem shocking, even repulsive.

Yet venerating relics remains far from a “relic” of the past. At the end of 2024, the skull of St. Thomas Aquinas – the great Dominican medieval thinker whose writings I study – made its first tour of the United States. The journey commemorated the “triple anniversary” of 700 years since his canonization, 750 years since his death and 800 years since his birth.

From Cincinnati to Rhode Island to Washington, D.C., thousands of Catholics turned out to pay their homage to this medieval saint.

Three women in nuns' habits, seen from the back, kneel at the front of a church, looking toward a small box on a pedestal.
Religious sisters venerating the skull at St. Patrick Church in Columbus, Ohio.
Nheyob/Wikimedia Commons

God’s dwelling place

What might Aquinas himself have thought about all the attention to his traveling skull – that fragile and now empty case for the brain behind one of the most productive minds of European philosophy?

Aquinas’ answer lies in a short but poignant text from “Summa Theologiae,” his best-known work. Christians should venerate relics, Aquinas says, because the saints’ bodies were dwelled in by God. The very parts of their bodies were the instruments, or “organs,” of God’s actions.

The saints as “organs” of God: What a riveting image! God is so intimately present to his friends, the saints, that their very bodies are sanctified by his presence. Those hands, now dead and desiccated, performed God’s own actions as they cared for the sick, fed the hungry, celebrated Mass and reconciled the lost sheep.

According to Aquinas, honoring saints’ relics is ultimately about honoring this divine activity, a superhuman love working through ordinary human beings. But as he notes elsewhere, God is present in all of creation, working “most secretly” through all creatures at every moment. So by recognizing the special holiness of saints’ relics, Christians can better perceive the universal holiness that radiates through the whole created world.

Cherished keepsakes

Yet in discussing relics, Aquinas has some challenging things to say about what is perhaps their most immediate draw: the sense that when I see or touch a relic, I am physically present to a saint.

Because the saints are brothers and sisters in the Christian family, he says, Christians should cherish their physical remains just as people cherish a memento of a loved one, like “a father’s coat or ring.”

I did a double-take when I read this: A memento? Surely the saint’s body is more than that.

A man in a white and purple robe, with a halo around his head, stands close to a crucified Christ, who seems to speak to him.
Stained glass in St. Patrick Church in Columbus, Ohio, depicts a mystical vision St. Thomas Aquinas had in the 13th century.
Nheyob/Wikimedia Commons, CC BY-SA

But Aquinas insists that physical remains really are more like mementos of the deceased than parts of them. When St. Teresa of Calcutta died, for instance, she left behind a corpse and a soul. These bodily remains shouldn’t be confused with the saint herself, who was a living, breathing, bodily person. If I kiss a saint’s relic, as Catholics often do, I am not kissing the saint but something that was formerly part of a saint. The word “relic” literally goes back to the Latin word for “leaving something behind.”

The holiness of a relic, then, derives from the person it was once part of, not what it is now.

Not just “once was,” though, but also “will be.” Aquinas adds – and to me this is one of the most beautiful aspects of his reflections on relics – that venerating a relic is also a way of looking forward to the future resurrection of the body. Christian doctrine teaches that at the end of time, God will restore each person’s body, reuniting it with their soul. Relics represent that hope for everlasting life.

Later this year, the skull formerly known as Aquinas’ will wend its way back to its permanent place of rest, buried under the altar of the Dominican church in Toulouse, France. During its visit to the U.S., I was down with pneumonia and never got a chance to pay my respects. But I cherish the “third class” relic that my sister-in-law mailed me from Cincinnati: a holy card that she had touched to the skull’s reliquary.The Conversation

Therese Cory, Associate Professor of Thomistic Studies, University of Notre Dame

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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