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Recently, a large number of Japanese macaques (Macaca fuscata) died of an unknown hemorrhagic syndrome at Kyoto University Primate Research Institute (KUPRI) and an external breeding facility for National Institute for Physiological Sciences (NIPS). We previously reported that the hemorrhagic syndrome of Japanese macaques at KUPRI was caused by infection with simian retrovirus 4 (SRV-4); however, the cause of similar diseases that occurred at the external breeding facility for NIPS was still unknown. In this study, we isolated SRV-5 from Japanese macaques exhibiting thrombocytopenia and then constructed an infectious molecular clone of the SRV-5 isolate. When the SRV-5 isolate was inoculated into two Japanese macaques, severe thrombocytopenia was induced in one of two macaques within 22 days after inoculation. Similarly, the clone-derived virus was inoculated into the other two Japanese macaques, and one of two macaques developed severe thrombocytopenia within 22 days. On the other hand, the remaining two of four macaques survived as asymptomatic carriers even after administering an immunosuppressive agent, dexamethasone. As determined by real-time PCR, SRV-5 infected a variety of tissues in Japanese macaques, especially in digestive and lymph organs. We also identified the SRV-5 receptor as ASCT2, a neutral amino acid transporter in Japanese macaques. Taken together, we conclude that the causative agent of hemorrhagic syndrome occurred at the external breeding facility for NIPS was SRV-5.

Background Removal of oral biofilm from the oral mucosa is essential for preventing risk of respiratory and gastrointestinal infection in elderly people. Currently, no device is available which can remove oral biofilm from oral mucosa effectively and safely. Therefore, the effectiveness and safety of the Micro Scale Mist UNIT (MSM-UNIT), a newly developed dental plaque removal device utilizing high speed sprays of fine water droplets, were evaluated for biofilm removal, including the rate and surface roughness for simulated tooth surface and mucous membrane. Methods Simulated tooth and oral mucosa coated with an artificial biofilm of Streptococcus mutans were used for evaluation of effectiveness, with uncoated substrates as the controls. The MSM-UNIT and a conventional air ablation device were operated under recommended instructions. The effectiveness was evaluated from the rate of removal of the biofilm, and the safety was evaluated from the damage observed by scanning electron microscope and surface roughness. Results The biofilm removal rate of the MSM-UNIT was significantly higher than that of AIRFLOW. Little damage was observed in the area treated by the MSM-UNIT. The surface roughness of the MSM-UNIT treated area on simulated tooth surface and oral mucosa showed no significant difference to the control area. In contrast, cracks and powder were observed in the area treated by AIRFLOW. In particular, the surface roughness of the AIRFLOW treated area for Toughsilon was significantly larger than that of the control. Conclusions The MSM-UNIT could be used safely and effectively for removing biofilm not only on simulated tooth surfaces but also simulated mucous membrane. The MSM-UNIT has no harmful effect on teeth or oral mucosa, and may be used for comprehensive oral care for patients during nursing care and the perioperative period.

Sequences homologous to human herpesvirus 6 (HHV-6) are integrated within the nuclear genome of about 1% of humans, but it is not clear how this came about. It is also uncertain whether integrated HHV-6 can reactivate into an infectious virus. HHV-6 integrates into telomeres, and this has recently been associated with polymorphisms affecting MOV10L1. MOV10L1 is located on the subtelomere of chromosome 22q (chr22q) and is required to make PIWI-interacting RNAs (piRNAs). As piRNAs block germline integration of transposons, piRNA-mediated repression of HHV-6 integration has been proposed to explain this association. In vitro, recombination of the HHV-6 genome along its terminal direct repeats (DRs) leads to excision from the telomere and viral reactivation, but the expected “solo-DR scar” has not been described in vivo. Here we screened for integrated HHV-6 in 7,485 Japanese subjects using whole-genome sequencing (WGS). Integrated HHV-6 was associated with polymorphisms on chr22q. However, in contrast to prior work, we find that the reported MOV10L1 polymorphism is physically linked to an ancient endogenous HHV-6A variant integrated into the telomere of chr22q in East Asians. Unexpectedly, an HHV-6B variant has also endogenized in chr22q; two endogenous HHV-6 variants at this locus thus account for 72% of all integrated HHV-6 in Japan. We also report human genomes carrying only one portion of the HHV-6B genome, a solo-DR, supporting in vivo excision and possible viral reactivation. Together these results explain the recently-reported association between integrated HHV-6 and MOV10L1/piRNAs, suggest potential exaptation of HHV-6 in its coevolution with human chr22q, and clarify the evolution and risk of reactivation of the only intact (non-retro)viral genome known to be present in human germlines., Author summary Human herpesvirus 6 (HHV-6) infects most people during childhood and can reactivate later in life to contribute to diseases. The HHV-6 genome is also inherited by about 1% of people, included in the end “cap” of one of their 46 chromosomes. Little is known about how HHV-6 genomes entered human genomes, whether or not they still do, and the risk this poses for virus reactivation. We looked for HHV-6 in genome sequences from ~7,500 Japanese people. Most integrated HHV-6 variants have been co-evolving with human chromosomes for many generations. Surprisingly, in almost three-fourths of Japanese people with HHV-6 in their genome, HHV-6 is integrated in the same end of the same chromosome – 22q. Persistence of the HHV-6 genome within the short “cap” that preserves the end of chromosome 22q raises the question of whether the integrated viral sequence has taken on a useful function for this chromosome. Some human genomes harbor only one part of the HHV-6 genome–the same part that remains after experimental HHV-6 reactivation, during which most of the virus is cut out of the genome. This suggests that integration of HHV-6 into inherited human genomes is not irreversible, and possibly leads to production of infectious virus.

The genome of human herpesvirus 6 (HHV-6) is integrated within the nuclear genome of about 1% of humans, but how this came about is not clear. HHV-6 integrates into telomeres, and this has recently been associated with polymorphisms affecting MOV10L1. MOV10L1 is located on the subtelomere of chromosome 22q (chr22q) and is required to make PIWI-interacting RNAs (piRNAs). piRNAs block integration of transposons in the germline, so piRNA-mediated repression of HHV-6 integration has been suspected. Whether integrated HHV-6 can reactive into an infectious virus is also uncertain. In vitro, recombination of the viral genome along its terminal direct repeats (DRs) leads to excision from the telomere and viral reactivation, but the expected single DR “scar” has not been described in vivo. We analyzed whole-genome sequencing (WGS) data from 13,040 subjects, including 7,485 from Japan. We found an association between integrated HHV-6 and polymorphisms on chr22q in Japanese subjects. However, association with the reported MOV10L1 polymorphism was driven by physical linkage to a single ancient endogenous HHV-6A variant integrated into the telomere of chr22q in East Asians. We resolved the junction of the human chromosome with this viral genome using long read sequencing. Unexpectedly, an HHV-6B variant has also endogenized in chr22q; two endogenous HHV-6 variants at this locus thus account for 72% of all integrated HHV-6 in Japan. We also report human genomes carrying only one portion of the HHV-6B genome, a single DR, supporting in vivo excision and viral reactivation. Using WGS data from North American families, we show that the incidence of HHV-6 integration into the germline is lower than its prevalence, and that integrated HHV-6 is not associated with the reported variant in MOV10L1. Together these results explain the recently reported association between integrated HHV-6 and MOV10L1/piRNAs, suggest exaptation of HHV-6 in its coevolution with human chr22q, and clarify the evolution and risk of reactivation of the only intact non-retroviral genome known to be present in human germlines.SIGNIFICANCE STATEMENTHuman herpesvirus 6 (HHV-6) infects most people during childhood, usually only causing fever and rash. Reactivation of HHV-6 has been linked to a number of neurological diseases including encephalitis, Alzheimer’s disease and multiple sclerosis. However, about 1% of people are born with the HHV-6 genome present within their genome, included in the end “cap” of one of their 46 chromosomes. Little is known about how and when HHV-6 genomes entered human genomes, whether or not they still do, and whether or not this poses risk for virus reactivation. We looked for HHV-6 in genome sequences from over 13,000 people. Most HHV-6 variants present in human genomes have been co-evolving with human chromosomes for many generations, and new integration events are rare. Surprisingly, in almost three fourths of Japanese people with HHV-6 in their genome, HHV-6 integrated in the same end of the same chromosome – 22q. Persistence of the HHV-6 genome within the short “cap” that preserves the end of chromosome 22q suggests that the integrated viral sequence may have taken on a useful function for this chromosome. We also found that some human genomes harbor only one part of the HHV-6 genome. This part is the same part that remains after experimental viral reactivation, during which most of the virus is cut out of the genome. This warrants assessment of the risk that integration of HHV-6 into inherited human genomes is not irreversible, and possibly leads to production of infectious virus.

Feline morbillivirus (FmoPV) is an emerging virus in cats, which is associated with tubulointerstitial nephritis. To study the in vitro host range of FmoPV, we inoculated FmoPV strain SS1 to 32 cell lines originated from 13 species and cultured for 2 weeks, followed by RNA extraction and reverse-transcription-polymerase chain reaction for FmoPV detection. As a result, only cell lines derived from cats and African green monkeys were susceptible to FmoPV. FmoPV infects diverse feline cell lines: epithelial, fibroblastic, lymphoid and glial cells. These results indicate that the receptor (s) for FmoPV are ubiquitously expressed in cats. No infectivity of FmoPV was observed in human cell lines, which suggests least threatening of cross-species transmission of FmoPV from cats to humans.

Feline morbillivirus (FmoPV) is an emerging virus in domestic cats and considered to be one of the causes of chronic renal failure in cats. In this study, we established a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for the detection of FmoPV. The results indicated that the detection limit of the assay was 10 50% tissue culture infective dose (TCID50)/ml in the original sample, and sensitivity of the assay was calculated as 0.12 TCID50 per one RT-LAMP reaction. We also detected FmoPV in clinical urine samples from cats infected with FmoPV. The FmoPV RT-LAMP assay is rapid, simple and highly specific for the detection of FmoPV, and thus, it would be a reliable detection method for FmoPV.

Feline morbillivirus (FmoPV) is an emerging virus that was recently discovered in domestic cats with chronic nephritis. Despite the potential role of FmoPV in chronic nephritis, little is known about its biological characteristics. In this study, we established a quantitative assay of FmoPV by using an indirect immunofluorescence technique. Viral titers of FmoPV were determined in one week. Treatment with polybrene® or trypsin which was previously used in virus isolation did not augment the virus titers. FmoPV was notably stable at 4°C, retaining high titers for at least 12 days. Heat-treatment at 60°C and 70°C effectively inactivated FmoPV in 10 and 2 min, respectively. The biological characteristics of FmoPV reported here will be beneficial for establishing an efficient virus isolation method and will provide important information to take a measure to reduce the risk of FmoPV infection.