Viruses

"A virus is a form of life with very simple requirements. The basic needs of a virus are a nucleic acid to be transmitted from generation to generation (the genome) and a messenger RNA to direct the synthesis of viral proteins. The critical viral proteins that the messenger RNA must encode are those that coat the genome and those that help replicate the genome. One of the great surprises of modern virology has been the discovery of the variety of genetic systems that viruses have evolved to satisfy their needs. Among the animal viruses, at least 6 totally different solutions to the basic requirements of a virus have been found."

"Autoimmune diseases, which are the third leading cause of morbidity in the industrialised world, afflict tens of millions in the United States. The idea that viruses can trigger autoimmunity in those with genetic predisposition through molecular mimicry has been simmering for a while. Viruses have been shown to have the potential to play a role in provoking and modifying the clinical manifestations of several auto-immune diseases, such as coxsackie virus in type 1 diabetes, coronaviruses in rheumatoid arthritis, and Epstein–Barr Virus in systemic autoimmune diseases. However, obtaining conclusive evidence of a connection between viral infection and subsequent autoimmune diseases is challenging, not only because it is frequently impossible to extract the virus from diseased tissues, but also because the collection of sufficient amounts of epidemiological evidence is constrained by lengthy process and geographic distances."

"Viruses play a significant role in the environmental factors that affect human immune system. Cytomegalovirus 28 and Epstein–Barr virus 6 are examples of viruses that have been linked to numerous autoimmune diseases, and now SARS-CoV-2 has the potential to be added to the list. The definite mechanisms underlying such phenomena are unknown. According to recent research, viruses can trigger autoimmunity through a number of different mechanisms, including molecular mimicry, epitope spreading, and bystander activation."

"Contrarily, there is also mounting evidence that viruses could play a protective role against autoimmunity, whereby viral infections trigger regulatory immune responses, which in turn prevent the onset of autoimmune reactions. It is reasonable that the dual impact of viral infections on autoimmunity is coordinated by different host, viral and environmental factors."

"Over the course of human history, scientists have identified only two instances of true virus superdodgers. That is, where a specific mutation in their genes makes people completely resistant to a virus. So that it slides off their cells, "like water sliding off a glass window," as Casanova puts it. In 2003, a team in London showed how some people never get a stomach bug, called norovirus, which causes vomiting and diarrhea. The researchers found that one mutation in their genes prevents them from making a molecule the virus needs to infect the cell. (In 1995, researchers in France figured out why some people appeared to never be infected with a species of malaria known as Plasmodium vivax. However, over the past decade, further studies have clarified that these superdodgers actually do become infected with the parasite; they simply don't show symptoms.)"

"When my colleagues and I discovered the first human retrovirus that causes a form of leukemia, a fatal neurological disease, the Journal of Virology rejected the paper. They more or less told me, "Bob, everybody knows it's not real — and go away." I said, "Wow." But then it got published in the Proceedings of the U.S. National Academy of Sciences."

"We learned that a virus freshly isolated from man or animal did not necessarily behave like the virus strain that we maintained in the laboratory, so-called tame virus, which might have been passaged through animals or tissue culture for generations. Virologists had to recognize that by transmission of a virus from animal to animal or from culture to culture over a period of time, what we ended up with through a process of natural selection or genetic selection was a virus adapted to growth in a new environment. A population of viruses is no more homogeneous than the human population; by passage, one culls out all of the inhomogeneous particles and leaves behind those which survive and grow so well,"

"In 1910 I described a malignant chicken sarcoma which could be propagated by transplanting its cells, these multiplying in their new hosts and forming new tumors of the same sort. In other ways the growth showed itself to be a neoplasm of a classical sort, yet, as reported in 1911, its cells yielded a causative virus. Numerous workers had already tried by then to get extraneous causes from transplanted mouse and rat tumors but the transferred cells had held their secret close. Hence the findings with the sarcoma were met with down-right disbelief, though soon several other, morphologically different, “spontaneous” chicken tumors were propagated by transplantation and from each a virus was got causing growths of its kind. Not until after some 15 years of disputation amongst oncologists were the findings with chickens deemed valid, and then they were relegated to a category distinct from that of mammals because from them no viruses could be obtained. Only in 1925, through the efforts of a British worker, W.E. Gye, was much attention given them by scientists."

"Why has it been so difficult to identify infectious agents as cancer-inducing factors in humans? Because there is no human pathogenic infectious agent causing cancer as the acute consequence of infection ... Infections linked to human cancers are common in human populations, most of them were present during the whole human evolution,and only a small proportion of infected individuals develops the respective cancer type ... Except for rare germline mutations, (XLLP), cancers linked to infection commonly occur decades after primary infection ..."

"We were preparing for something like this as it's not a matter of if, it is a matter of when."

"... microcephaly is only one possible adverse outcome among a spectrum of conditions that may be part of congenital Zika syndrome. A population-level increase in central nervous system anomalies has been observed in both French Polynesia and Brazil."

"The current Zika virus (ZIKV) outbreak is associated with neurological malformations and disorders in neonates. Areas of increased incidence of malformations may overlap with dengue-hyperendemic areas. ZIKV infection is enhanced by antibodies against dengue virus (DENV) in cell culture and inbred mice. Sufficiently powered clinical studies or primate studies addressing the enhancement of fetal ZIKV infection after previous dengue infection are not available. The human placenta is susceptible to ZIKV in vitro, but it is unknown whether antibody-dependent enhancement of ZIKV infection occurs at the placental barrier. Here we studied ZIKV infection in placental tissue in the presence of DENV-immune sera. Explants from the amniochorionic membrane, the chorionic villi, and the maternal decidua were infected with ZIKV in the presence of DENV type 1-, 2-, or 4-immune sera, or controls. Presence of DENV antibodies of any type enhanced the percentage of successful infections of organ explants between 1.42- and 2.67-fold, and led to a faster replication as well as significantly increased virus production. No enhancement was seen with yellow fever or chikungunya virus control sera. Pre-existing DENV antibodies may pose an increased risk of trans-placental ZIKV transmission."

"Zika virus (ZIKV) was discovered in Africa in 1947 and was first detected in Asia in 1966, yet its potential effect on public health was not recognized until the virus caused outbreaks in the Pacific from 2007 to 2015 and began spreading throughout the Americas in 2015. ... The ability of ZIKV to cause congenital defects in fetuses and infants, as exemplified by the microcephaly epidemic in Brazil, is an unprecedented feature in a mosquito-borne viral infection. ... Although transmission of ZIKV has declined in the Americas, outbreaks and infection clusters continue to occur in some regions, such as India and Southeast Asia, where there are large populations of women of childbearing age who are susceptible to the virus."

"The Zika virus protease NS2B-NS3 catalyses the processing of the viral precursor polyprotein as an essential step during viral replication. Since the epidemic Zika virus outbreak in the Americas, several inhibitors of this protease have been reported. Substrate-derived peptides revealed important structural information about the active site, whilst more drug-like small molecules have been discovered as allosteric inhibitors."

"We recently developed a chimeric flavivirus vaccine technology based on the novel insect-specific Binjari virus (BinJV) and used this to generate a chimeric ZIKV vaccine (BinJ/ZIKA-prME) that protected IFNAR-/- dams and fetuses from infection. Herein, we show that a single vaccination of IFNAR-/- mice with unadjuvanted BinJ/ZIKA-prME generated neutralizing antibody responses that were retained for 14 months. At 15 months post vaccination, mice were also completely protected against detectable viremia and substantial body weight loss after challenge with ZIKVPRVABC59. BinJ/ZIKA-prME vaccination thus provided long-term protective immunity without the need for adjuvant or replication of the vaccine in the vaccine recipient, both attractive features for a ZIKV vaccine."

"... tobacco mosaic virus ... it's been used as a model for more than fifty years, and scientists throughout the world have used it for a variety of studies."

"The interest in plant virus evolution can be dated to the late 1920s, when it was shown that plant virus populations were genetically heterogeneous, and that their composition changed according to the experimental conditions. Many important ideas were generated prior to the era of molecular virology, such as the role of hostand vector-associated selection in virus evolution, and also that small populations, gene coadaptation and evolutionary trade-offs could limit the efficiency of selection. The analysis of viral genomes in the 1980s and 1990s established the quasispecieslike structure of their populations and allowed extensive analyses of the relationships among virus strains and species. The concept that virus populations had huge sizes and high rates of adaptive mutations became prevalent in this period, with selection mostly invoked as explaining observed patterns of population structure and evolution. In recent times virus evolution has been coming into line with evolutionary biology, and a more complex scenario has emerged."

"Plants have been explored for many years as inexpensive and versatile platforms for the generation of vaccines and other biopharmaceuticals. Plant viruses have also been engineered to either express subunit vaccines or act as epitope presentation systems. Both icosahedral and helical, filamentous-shaped plant viruses have been used for these purposes. More recently, plant viruses have been utilized as nanoparticles to transport drugs and active molecules into cancer cells. The following review describes the use of both icosahedral and helical plant viruses in a variety of new functions against cancer."

"The discovery of the first non-cellular infectious agent, later determined to be tobacco mosaic virus, paved the way for the field of virology. In the ensuing decades, research focused on discovering and eliminating viral threats to plant and animal health. However, recent conceptual and methodological revolutions have made it clear that viruses are not merely agents of destruction but essential components of global ecosystems. As plants make up over 80% of the biomass on Earth, plant viruses likely have a larger impact on ecosystem stability and function than viruses of other kingdoms. Besides preventing overgrowth of genetically homogeneous plant populations such as crop plants, some plant viruses might also promote the adaptation of their hosts to changing environments. However, estimates of the extent and frequencies of such mutualistic interactions remain controversial."

"Persistent infection, wherein a pathogen is continually present in a host individual, is widespread in virus–host systems. However, little is known regarding how seasonal environments alter virus–host interaction during such metastability. We observed a lineage-to-lineage infection of the host plant Arabidopsis halleri with Turnip mosaic virus for 3 years without severe damage. Virus dynamics and virus–host interactions within hosts were highly season dependent. Virus accumulation in the newly formed leaves was temperature dependent and was suppressed during winter. Transcriptome analyses suggested that distinct defence mechanisms, i.e. salicylic acid (SA)-dependent resistance and RNA silencing, were predominant during spring and autumn, respectively. Transcriptomic difference between infected and uninfected plants other than defence genes appeared transiently only during autumn in upper leaves. However, the virus preserved in the lower leaves is transferred to the clonal offspring of the host plants during spring. In the linage-to-linage infection of the A. halleri–TuMV system, both host clonal reproduction and virus transmission into new clonal rosettes are secured during the winter–spring transition. How virus and host overwinter turned out to be critical for understanding a long-term virus–host interaction within hosts under temperate climates, and more generally, understanding seasonality provides new insight into ecology of plant viruses."

"When the genetic material of a highly virulent bacteriophage penetrates a bacterium, the bacterial chromosome is disintegrated and the bacterium consequently becomes incapable of producing messengers and bacterial proteins. The DNA of the bacteriophage synthesizes its own messengers with the aid of s synthesized by its host and of the enzymes of its host. The messengers of the bacteriophage will establish themselves on the bacterial s. With the aid of the activated and of the bacterial enzymes, the proteins of the bacteriophage are synthesized. Some of these proteins are enzymes necessary, for example, for the manufacture of specific constituents of the phages such as . Others are enzymes necessary for the replication of the bacteriophage DNA. Still others are structural proteins of the . One of the last to be formed is endolysine, which destroys the wall of the bacterium, provokes its rupture, and ensures the liberation of the virions. When we examine the kinetics of production of the various proteins, we find that each is formed in a given period of the evolutionary cycle. Everything takes place as if a system of sequential repression and derepression was acting."

"Bacterial CRISPR-Cas systems utilize sequence-specific RNA-guided nucleases to defend against bacteriophage infection. As a countermeasure, numerous phages are known that produce proteins to block the function of class 1 CRISPR-Cas systems. However, currently no proteins are known to inhibit the widely used class 2 CRISPR-Cas9 system. To find these inhibitors, we searched cas9-containing bacterial genomes for the co-existence of a CRISPR spacer and its target, a potential indicator for CRISPR inhibition. This analysis led to the discovery of four unique type II-A CRISPR-Cas9 inhibitor proteins encoded by Listeria monocytogenes prophages. More than half of L. monocytogenes strains with cas9 contain at least one prophage-encoded inhibitor, suggesting widespread CRISPR-Cas9 inactivation. Two of these inhibitors also blocked the widely used Streptococcus pyogenes Cas9 when assayed in Escherichia coli and human cells. These natural Cas9-specific “anti-CRISPRs” present tools that can be used to regulate the genome engineering activities of CRISPR-Cas9."

"Bacteriophage (phage) therapy, i.e., the use of viruses that infect bacteria as antimicrobial agents, is a promising alternative to conventional antibiotics. Indeed, resistance to antibiotics has become a major public health problem after decades of extensive usage. However, one of the main questions regarding phage therapy is the possible rapid emergence of phage-resistant bacterial variants, which could impede favourable treatment outcomes. Experimental data has shown that phage-resistant variants occurred in up to 80% of studies targeting the intestinal milieu and 50% of studies using sepsis models. Phage-resistant variants have also been observed in human studies, as described in three out of four clinical trials that recorded the emergence of phage resistance. On the other hand, recent animal studies suggest that bacterial mutations that confer phage-resistance may result in fitness costs in the resistant bacterium, which, in turn, could benefit the host. Thus, phage resistance should not be underestimated and efforts should be made to develop methodologies for monitoring and preventing it."

"Increasing reports of antimicrobial resistance and limited new antibiotic discoveries and development have fuelled innovation in other research fields and led to a revitalization of bacteriophage (phage) studies in the Western world. Phage therapy mainly utilizes obligately lytic phages to kill their respective bacterial hosts, while leaving human cells intact and reducing the broader impact on commensal bacteria that often results from antibiotic use. Phage therapy is rapidly evolving and has resulted in cases of life-saving therapeutic use and multiple clinical trials. However, one of the biggest challenges this antibiotic alternative faces relates to regulations and policy surrounding clinical use and implementation beyond compassionate cases. This review discusses the multi-drug resistant Gram-negative pathogens of highest critical priority and summarizes the current state-of-the-art in phage therapy targeting these organisms."

"We have identified previously unsuspected, directly pathogenic roles for bacteriophage (phage) virions in bacterial infections. In particular, we report that internalization of phage by human and murine immune cells triggers maladaptive viral pattern recognition receptors and suppressed bacterial clearance from infected wounds."

"Despite the fact that phages were recognized early to be extremely abundant in the biosphere, existing in all environments where bacteria occur, only very little research was targeted to understand their ecological roles (Summers, 2012). Even today, studies about the role of bacterial viruses in most complex ecosystems are uncommon and the impact of bacterial viruses on cohabitating microorganisms is little appreciated (Rohwer et al., 2009). While knowledge of environmental bacteriophages has increased in the last 10 years (Miller, 2001; Muniesa et al., 2013), there is still much to learn about their roles in even the most widely-studied environments such as the rhizosphere, phyllosphere, and human gut. It will be through such work that we might more wisely use phages in medical and technological applications."

"An announcement on the new name would be made "as soon as possible", said Tedros."

"The probability of containment is diminishing daily. It's really unfortunate because we do have the tools. This is not an unknown virus. … We have vaccines that are already available, even vaccines with indications for monkeypox. Therapeutics. And we know what's needed to be done."

"Right now we just don't have nearly enough vaccine to even begin to have a measurable impact on widespread global transmission. There's going to be a lot of frustrated people who want to get vaccine where it won't be available."

"Declaring a PHEIC makes governments and the global public sit up and take notice. It raises the political stakes for government leaders, and it raises the level of accountability for them to act."

"Public health officials reject comparisons to the early days of the coronavirus pandemic, when they mandated masks and shut down public spaces. They noted that the novel coronavirus was unfamiliar, far deadlier and airborne, with hospitals overrun with patients at various points over the past two years. Monkeypox has known treatments and vaccines, although they have been challenging to access; it also has not killed anyone in the United States, and hospitalizations are uncommon."

"We are prepared to take our response to the next level in addressing this virus and we urge every American to take monkeypox seriously."