Human parainfluenza virus type 1 regulates cholesterol biosynthesis and establishes quiescent infection in human airway cells.

Human parainfluenza virus type 1 (hPIV1) and 3 (hPIV3) cause seasonal epidemics, but little is known about their interaction with human airway cells. In this study, we determined cytopathology, replication, and progeny virion release from human airway cells during long-term infection in vitro. Both viruses readily established persistent infection without causing significant cytopathic effects. However, assembly and release of hPIV1 rapidly declined in sharp contrast to hPIV3 due to impaired viral ribonucleocapsid (vRNP) trafficking and virus assembly. Transcriptomic analysis revealed that both viruses induced similar levels of type I and III IFNs. However, hPIV1 induced specific ISGs stronger than hPIV3, such as MX2, which bound to hPIV1 vRNPs in infected cells. In addition, hPIV1 but not hPIV3 suppressed genes involved in lipid biogenesis and hPIV1 infection resulted in ubiquitination and degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, a rate limiting enzyme in cholesterol biosynthesis. Consequently, formation of cholesterol-rich lipid rafts was impaired in hPIV1 infected cells. These results indicate that hPIV1 is capable of regulating cholesterol biogenesis, which likely together with ISGs contributes to establishment of a quiescent infection.

Mitigation of Memory Impairment in Ovariectomized Rats Using Garlic Powder Treated with Subcritical Water.

Women with estrogen deficiency are at the risk of suffering from neurological symptoms such as memory impairment. In the present study, we investigated the effect of garlic, Allium sativum L. (Asparagales: Amaryllidaceae), treated with subcritical water on memory impairment in ovariectomized (OVX) rats. OVX rats were administered garlic powder for 84 d. Hippocampus-dependent spatial memory was assessed using the Morris water maze test. Escape latency of the OVX rats increased compared with that of sham-operated rats. The prolonged escape latency of the OVX rats decreased to the level of that of sham-operated rats upon the administration of garlic powder (0.5% in feed). The weights of the body, uterus, and brain were not affected by the garlic powder administration. These results suggest that garlic powder treated with subcritical water mitigates memory impairment in OVX rats.

[Analysis and Control of Viral Infection Mechanisms by Glycobiology].

Glycans are present in all living organisms, including viruses, bacteria, and animals, and perform various biological functions. The author has been studying influenza viruses' glycan usage mechanisms, particularly the functional analysis of neuraminidase (NA), a viral sialidase. The authors recently focused on influenza virus NAs' high sialidase activity with the aim of using sialidase activity detection as a virus detection technology. Using the probe BTP3-Neu5Ac, allows fluorescent imaging of sialidase activity, we created a new technique for easy, rapid, and high sensitivity fluorescent imaging of virus-infected cells. The detection of viruses using BTP3-Neu5Ac does not require specific antibodies and can be performed by simply adding reagents. Furthermore, fluorescence imaging of sialidase as a virus detection technology has many advantages, including isolating viruses from fluorescently imaged infected cells. This detection technique is easy to use in basic research and hygiene testing, where viral culture is conducted and is expected to be widely used.

Protein-bound sialic acid in saliva contributes directly to salivary anti-influenza virus activity.

The oral cavity is an entrance for respiratory viruses, such as influenza. Recently, saliva has been shown to exert both antimicrobial and antiviral activities. Thus, saliva may be a biological factor that contributes to the prevention of influenza infection. However, the actual salivary anti-influenza A virus (IAV) activity in individuals and its determinant factors are unknown. By assessing individual variations in salivary anti-IAV activity in 92 people using an established new high-throughput system in this study, we found that the anti-IAV activity varied widely between individuals and showed a significant positive correlation with protein-bound sialic acid (BSA) level (ρ = 0.473; p < 0.001). Furthermore, the anti-IAV activity of saliva with enzymatically reduced BSA content was significantly lower. These results indicate that BSA is a direct regulator of salivary anti-IAV activity and is a determinant of individual differences. Additionally, after comparing the anti-IAV activity across the groups by age, anti-IAV activity in young people (aged 5-19 years) were lower than in adults aged 20-59 years and elderly people aged 60-79 years. Our study suggests that BSA levels in saliva may be important in preventing influenza infection.

Key Role of the Influenza A Virus PA Gene Segment in the Emergence of Pandemic Viruses.

Influenza A viruses (IAVs) are a significant human pathogen that cause seasonal epidemics and occasional pandemics. Avian waterfowl are the natural reservoir of IAVs, but a wide range of species can serve as hosts. Most IAV strains are adapted to one host species and avian strains of IAV replicate poorly in most mammalian hosts. Importantly, IAV polymerases from avian strains function poorly in mammalian cells but host adaptive mutations can restore activity. The 2009 pandemic H1N1 (H1N1pdm09) virus acquired multiple mutations in the PA gene that activated polymerase activity in mammalian cells, even in the absence of previously identified host adaptive mutations in other polymerase genes. These mutations in PA localize within different regions of the protein suggesting multiple mechanisms exist to activate polymerase activity. Additionally, an immunomodulatory protein, PA-X, is expressed from the PA gene segment. PA-X expression is conserved amongst many IAV strains but activity varies between viruses specific for different hosts, suggesting that PA-X also plays a role in host adaptation. Here, we review the role of PA in the emergence of currently circulating H1N1pdm09 viruses and the most recent studies of host adaptive mutations in the PA gene that modulate polymerase activity and PA-X function.