Measles Virus Infection

Individuals inhale measles virus particles in aerosols and it is currently thought that these particles infect the cells that line the airways (respiratory epithelial cells) before being passed to immune cells that carry the virus particles to other parts of the body and then back to the airways, which again become infected and shed virus into exhaled aerosols.  In the study, a measles virus unable to bind to and infect epithelial cells was found to cause symptoms of measles virus infection in monkeys even though it did not infect respiratory epithelial cells and was not being shed into exhaled aerosols.  These data suggest that, in fact, inhaled measles virus particles first infect lymphocytes and are only passed to respiratory epithelial cells from the lymphocytes in the tissues.  Further, they indicate that the protein that measles virus particles bind to on respiratory epithelial cells, which has yet to be identified, is likely to be found on the surface of the cells that faces the tissues rather than the surface that faces the airways, as previously assumed.  As discussed in an accompanying commentary by Makoto Takeda, at Kyushu University, Japan, the results of this study should help researchers identify this protein.

Coronavirus Replication and Protein Secretion in Infected Cells

Coronaviruses, a group including the well-known SARS virus, are the causative agents of many respiratory and enteric infections in humans and animals. As with all viruses, virtually every step of their infection cycle depends on host cellular factors. As the first, most crucial step after their penetration into cells, coronaviruses assemble huge RNA replication “factory” complexes in association with characteristic, newly induced double membrane vesicles. The cellular pathways hijacked by these plus-strand RNA viruses to create these “factories” have thus far not been elucidated.

The researchers, led by Cornelis A. M. de Haan, showed that RNA replication of mouse hepatitis coronavirus (MHV) was inhibited by a drug — brefeldin A — that disrupts the central station in the cell’s secretory pathway, the Golgi complex. Consistently, depletion of both the cellular target of brefeldin A, a factor called GBF1, and its downstream target, ARF1, was also shown to negatively affect coronavirus infection.

The researchers conclude that “an intimate association exists between the early secretory pathway and MHV replication.” They speculate that, while GBF1 and ARF1 are not involved in the formation of the viral replication structures, they probably play a key role in their maturation or functioning. As this work was limited to the mouse hepatitis coronavirus, an interesting next step would be to study the importance of GBF1 and ARF1 in the replication of other coronaviruses.

Brain Damaging Disease Molecular Changes in Brain Fluid

Soon after an individual becomes infected with HIV the virus infects cells in the brain and spinal cord (the central nervous system [CNS]).  Although this causes no immediate problems, during the late-stages of disease it can cause dementia and encephalitis (acute inflammation of the brain that can cause death).  Monkeys infected with a relative of HIV (SIV) also sometimes develop CNS damage and provide a good model of CNS disease in individuals infected with HIV.  Insight into the mechanisms of CNS damage in SIV-infected monkeys has now been provided by a team of researchers at The Scripps Research Institute, La Jolla, who developed an approach to identify molecular changes in the fluid bathing the CNS (the CSF).  The researchers, who were led by Howard Fox and Gary Siuzdak, hope that similar approaches could be used to provide new information about other neurodegenerative and neuropsychiatric disorders.

In the study, an approach known as global metabolomics was used to assess the levels of molecules known as metabolites in the CSF before and after SIV-induced encephalitis was manifest.  The level of a number of metabolites, including some known as fatty acids and phospholipids, was observed to increase during infection.  Consistent with this, a protein known to be important in the generation of fatty acids was found to be increased in the brain of monkeys with SIV-induced encephalitis.  Further studies will be required to determine the precise role of the increased level of each metabolite, but it should be noted that many of them are known to induce receptor signaling and thereby might be able to further modulate CNS function.

Infection Control Intervention Helps Keep Kids in School

A study from researchers at Children’s Hospital Boston published in Pediatrics found that a simple infection control intervention in elementary schools – disinfecting frequently-touched surfaces and using alcohol-based hand sanitizers – helped reduce illness-related student absenteeism.Illnesses caused by bacteria and viruses account for millions of lost school days each year.(1) According to Thomas Sandora, MD, MPH, a pediatric infectious diseases specialist at Children’s Hospital Boston, “The best ways to avoid common infections are cleaning your hands and preventing exposure to the germs that cause these illnesses. Our research indicates that elementary schools should consider a few simple infection control practices to help keep students healthier.”

The study, led by Dr. Sandora, was a randomized, controlled trial involving 285 third-, fourth-, and fifth-grade students in an elementary school system in Avon, Ohio. Teachers in intervention classrooms used disinfecting wipes on student desks, and students used hand sanitizer in the classroom at key points throughout the school day. Control classrooms followed usual hand washing and cleaning procedures.

Over eight weeks, researchers tracked the frequency of absences and the reasons for missing school. Study investigators also tested several classroom surfaces for total bacterial counts and for the presence of several common viruses.

Researchers found absenteeism rates for gastrointestinal illnesses were nine percent lower in classrooms that followed the infection control regimen of disinfecting surfaces and using alcohol-based hand sanitizers. The absenteeism rate for respiratory illness was not affected by this intervention.

Gastrointestinal illnesses are extremely common for school-age children, and children can be at risk for these infections because of frequent exposure to ill peers and poor hand hygiene.(1) In fact, the bacteria and viruses that cause these gastrointestinal infections can be easily passed from one person to another on the hands.(2) The germs can also survive on surfaces in the environment, where some of them can persist for hours to days.(1)

The study suggests that schools should consider adopting simple infection control practices, including disinfecting desktops once a day and using hand sanitizer before and after lunch, to help reduce days lost to common illnesses.

Artificial Viruses Carry Genes and Drug Molecules into Tumor Cells

Viruses are true experts at importing genetic material into the cells of an infected organism. This trait is now being exploited for gene therapy, in which genes are brought into the cells of a patient to treat genetic diseases or genetic defects. Korean researchers have now made an artificial virus. As described in the journal Angewandte Chemie, they have been able to use it to transport both genes and drugs into the interior of cancer cells.

Natural viruses are extremely effective at transporting genes into cells for gene therapy; their disadvantage is that they can initiate an immune response or cause cancer. Artificial viruses do not have these side effects, but are not especially effective because their size and shape are very difficult to control—but crucial to their effectiveness. A research team headed by Myongsoo Lee has now developed a new strategy that allows the artificial viruses to maintain a defined form and size.

The researchers started with a ribbonlike protein structure (β-sheet) as their template. The protein ribbons organized themselves into a defined threadlike double layer that sets the shape and size. Coupled to the outside are “protein arms” that bind short RNA helices and embed them. If this RNA is made complementary to a specific gene sequence, it can very specifically block the reading of this gene. Known as small interfering RNAs (siRNA), these sequences represent a promising approach to gene therapy.

Glucose building blocks on the surfaces of the artificial viruses should improve binding of the artificial virus to the glucose transporters on the surfaces of the target cells. These transporters are present in nearly all mammalian cells. Tumor cells have an especially large number of these transporters.

Trials with a line of human cancer cells demonstrated that the artificial viruses very effectively transport an siRNA and block the target gene.

In addition, the researchers were able to attach hydrophobic (water repellant) molecules—for demonstration purposes a dye—to the artificial viruses. The dye was transported into the nuclei of tumor cells. This result is particularly interesting because the nucleus is the target for many important antitumor agents.