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Effect of Loss-of-function of the herpes Simplex Virus-1 microRNA H6-5p on Virus Replication

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Virologica Sinica 2019年第4期34卷 386-396页

作者： Rongquan Huang Xusha Zhou Shuqi Ren Xianjie Liu Zhiyuan Han Grace Guoying Zhou School of Basic Medical Sciences Guangzhou Medical UniversityGuangzhou 511436China Shenzhen International Institute for Biomedical Research Shenzhen 518116China

To date, 29 distinct microRNAs(miRNAs) have been reported to be expressed during herpes simplex virus infections.Sequence analysis of mature herpes simplex virus-1(HSV-1) miRNAs revealed five sets of miRNAs that are complementary to each other: miR-H6-5p/H1-3p, miR-H6-3p/H1-5p, H2-5p/H14-3p, miR-H2-3p/H14-5p, and miR-H7/H27.However, the roles of individual miRNAs and consequences of this complementarity remain unclear. Here, we focus on two of these complementary miRNAs, miR-H6-5p and miR-H1-3p, using loss-of-function experiments in vitro and in a mouse model of infection using an miRNA sponge approach, including tandem multiplex artificial miRNA-binding sequences that do not match perfectly to the target miRNA inserted downstream of a green fluorescent protein reporter gene. Infection with recombinant virus expressing the miR-H6-5p sponge reduced viral protein levels and virus yield.Decreased accumulation of viral proteins was also observed at early stages of infection in the presence of both an miR-H6-5p inhibitor and plasmid-expressed miR-H1-3p. Moreover, establishment of latency and reactivation did not differ between the recombinant virus expressing the miR-H6-5p sponge and wild-type HSV-1. Taken together, these data suggest that miR-H6-5p has an as-yet-unidentified role in the early stages of viral infection, and its complement miR-H1-3p suppresses this role in later stages of infection. This report extends understanding of the roles of miRNAs in infection by herpes simplex viruses, supporting a model of infection in which the production of virus and its virulent effects are tightly controlled to maximize persistence in the host and population.

关键词： miR-H6-5p miR-H1-3p Sponge Replication herpes simplex virus-1(HSV-1)

Inhibition of herpes Simplex Virus-1 Replication by Natural Compound Honokiol

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Virologica Sinica 2019年第3期34卷 315-323页

作者： Shuai Liu Long Li Lingbing Tan Xiaozhen Liang University of Chinese Academy of Sciences Chinese Academy of SciencesBeijing 100039China Key Laboratory of Molecular Virology & Immunology Institut Pasteur of ShanghaiShanghai 200031China

Honokiol is a pleiotropic natural compound isolated from Magnolia and has multiple biological and clinically relevant effects,including anticancer and antimicrobial function.However,the antiviral activity of honokiol has not yet been well studied.Here we showed that honokiol had no effect on herpes simplex virus-1(HSV-1)entry,but inhibited HSV-1 viral DNA replication,gene expression and the production of new progeny viruses.The combination of honokiol and clinical drug acyclovir augmented inhibition of HSV-1 infection.Our results illustrate that honokiol could be a potential new candidate for clinical consideration in the treatment of HSV-1 infection alone or combination with other therapeutics.

关键词： Honokiol herpes simplex virus-1(HSV-1) Viral replication Anti-viral activity Acyclovir

Disturbed Yin-Yang balance:stress increases the susceptibility to primary and recurrent infections of herpes simplex virus type 1

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Acta Pharmaceutica Sinica B 2020年第3期10卷 383-398页

作者： Chang Yan Zhuo Luo Wen Li Xue Li Robert Dallmann Hiroshi Kurihara Yi-Fang Li Rong-Rong He Guangdong Engineering Research Center of Chinese Medicine&Disease Susceptibility Jinan University Guangzhou 510632China International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education(MOE) School of PharmacyJinan UniversityGuangzhou 510632China Institute of Atmospheric Environmental Safety and Pollution Control Jinan UniversityGuangzhou 510632China Warwick Medical School University of WarwickCoventry CV47ALUK

herpes simplex virus type 1(HSV-1),a neurotropic herpes virus,is able to establish a lifelong latent infection in the human host.Following primary replication in mucosal epithelial cells,the virus can enter sensory neurons innervating peripheral tissues via nerve termini.The viral genome is then transported to the nucleus where it can be maintained without producing infectious progeny,and thus latency is established in the cell.Yin-Yang balance is an essential concept in traditional Chinese medicine(TCM)theory.Yin represents stable and inhibitory factors,and Yang represents the active and aggressive factors.When the organism is exposed to stress,especially psychological stress caused by emotional stimulation,the Yin-Yang balance is disturbed and the virus can re-engage in productive replication,resulting in recurrent diseases.Therefore,a better understanding of the stress-induced susceptibility to HSV-1 primary infection and reactivation is needed and will provide helpful insights into the effective control and treatment of HSV-1.Here we reviewed the recent advances in the studies of HSV-1 susceptibility,latency and reactivation.We included mechanisms involved in primary infection and the regulation of latency and described how stress-induced changes increase the susceptibility to primary and recurrent infections.

关键词： herpes simplex virus type 1 HSV-1 Susceptibility Latency Reactivation Stress

Transcriptional regulation of the herpes Simplex Virus 1α-gene by the viral immediate-early protein ICP22 in association with VP16

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Science China(Life Sciences) 2009年第4期52卷 344-351页

作者： CUN Wei, GUO Lei, ZHANG Ying, LIU LongDing, WANG LiChun, LI JianFeng, DONG ChengHong, WANG JinJin & LI QiHan Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China Institute of Medical Biology Chinese Academy of Medical Sciences and Peking Union Medical College Kunming China

herpes Simplex Virus 1 (HSV1) is capable of inducing two forms of infection in individuals, and the establishment of which type of infection occurs is linked to the transcriptional activation of viral α genes. One of the HSV1 α genes, ICP22, is known to have multiple functions during virus replication, but its distinct roles are still unclear. This study showed that ICP22 functions as a general repressor for certain viral and cellular promoters, and this transcriptional repression by ICP22 is independent of the specific upstream promoter element, as shown using the CAT enzyme assay system. Further work also found that VP16 interfered with ICP22 mediated transcriptional repression of the viral α4 gene, through interactions with specific elements upstream of the α4 gene promoter. These findings support the possibility that ICP22 and VP16 control transcription of HSV1α genes in a common pathway for the establishment of either viral lytic or latent infections.

关键词： herpes simplex virus ICP22 transcription VP16 α gene

Systemic IL-1β production as a consequence of corneal HSV-1 infection-contribution to the development of herpes simplex keratitis

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International Journal of Ophthalmology(English edition) 2019年第9期12卷 1493-1497页

作者： Joan NíGabhann-Dromgoole Ciaran de Chaumont David Shahnazaryan Siobhán Smith Conor Malone Jaythoon Hassan Cillian F.De Gascun Caroline A.Jefferies Conor C.Murphy Molecular and Cellular Therapeutics and RSCI Research Institute Royal College of Surgeons in IrelandDublin 2Ireland Department of Ophthalmology Royal College of Surgeons in IrelandDublin 2Ireland Department of Ophthalmology Royal Victoria Eye and Ear HospitalDublin 2Ireland National Virus Reference Laboratory University College DublinBelfieldDublin 4Ireland Department of Medicine Division of Rheumatology and Department of Biomedical SciencesCedars-Sinai Medical CentreLos AngelesCA 90048USA

This study sought to identify potential therapeutic targets in herpes simplex keratitis(HSK) patients with active and inactive infection by investigating peripheral cytokine production. Peripheral blood mononuclear cells(PBMCs) and serum were prepared from healthy controls and HSK patients during active infection or following treatment(inactive infection). Serum antibody titres were determined by ELISA. Protein expression levels were analysed by Western blot. Cytokine levels were determined by multiplex ELISA. Active corneal herpes simplex virus type 1(HSV-1) infection resulted in significantly elevated peripheral levels of IL-1β in HSK patients compared to healthy controls, and remained significantly increased following treatment. Elevated production of IL-1β in inactive patients was associated with significantly increased levels of IRF3 and STAT1, key proteins involved in promoting anti-viral immune responses. Our data suggest that inflammation persists beyond the period that it is clinically evident and that enhanced peripheral production of IL-1β may have implications for HSV-1 viral clearance in active and inactive HSK patients.

关键词： herpes simplex virus type 1 herpes simplex keratitis inflammation peripheral immune response pathogenesis

Intestinal pseudo-obstruction caused by herpes zoster:Case report and pathophysiology

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World Journal of Clinical Cases 2018年第6期6卷 132-138页

作者： Roberto Anaya-Prado José V Pérez-Navarro Ana Corona-Nakamura Michelle M Anaya-Fernández Roberto Anaya-Fernández Marian Eliza Izaguirre-Pérez Department of Surgery at Western Medical Center the Mexican Institute of Social Security Division of Research at Autonomous University of Guadalajara Department of Infectious Diseases at Western Medical Center the Mexican Institute of Social Security Division of Research at University of Guadalajara

herpes zoster(HZ) infection occurs in approximately 10% to 30% of individuals. Visceral neuropathies secondary to HZ can cause cystitis and urinary retention. But colonic pseudo-obstruction can also occur. Peripheral neuropathy may reveal segmental motor paresis of either upper or lower limbs, the abdominal muscles or the diaphragm. We report the case of a 62-year-old male patient who presented with abdominal distention and cutaneous vesicular eruption on the left side of the abdominal wall. Plain X-rays and computed tomography scan showed distended small bowel. A diagnosis of intestinal pseudo-obstruction was made secondary to segmental paresis of the small intestine and visceral neuropathy. Conservative management was successful and the patient was discharged uneventfully. Intestinal pseudo-obstruction ought to be consideredwhen dealing with non-obstructive(adynamic) conditions of the digestive tract associated with HZ infection; since early recognition may help to avoid unnecessary surgery.

关键词： Ogilvie’s symdrome herpes zoster virus Neuropathies Intestinal pseudo-obstruction

Functional analysis of transcriptional regulation of herpes simplex virus type 1 tegument protein VP22

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Science China(Life Sciences) 2008年第11期51卷 966-972页

作者： YU Xian1,2, LI WeiZhong1, LIU LongDing1, CHE YanChun1, CUN Wei1, WU WenJuan1, HE ChunYan1, SHAO CongWen1 & LI QiHan1 1 Department of Viral Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China 2 Institute of Materia Medica, North Sichuan Medical College, Nanchong 637007, China Department of Viral Immunology Institute of Medical Biology Chinese Academy of Medical Sciences and Peking Union Medical College Kunming China Institute of Materia Medica North Sichuan Medical College Nanchong China

The herpes simplex virus type 1 (HSV-1) tegument proteins have important functions in the viral repli- cation process. In order to investigate the role of the HSV-1 tegument protein VP22 in viral replication, its transcriptional regulation of viral promoters was investigated using the chloramphenicol acetyl- transferase (CAT) assay. The results indicate that VP22 exerts a dose-dependent transcriptional in- hibitory effect on the HSV-1 α4, TK, and gC gene promoters. VP22 had the capacity to repress tran- scriptional activation of promoters via different viral transcription regulatory factors such as VP16 and ICP0, as evidenced by the specific repression of the TK and gC gene promoters by ICP0. In addition, VP22 was capable of inhibiting the promotion of ICP0 transcriptional activation in the presence of HAT PCAF, which is even more remarkable than the VP22 repression of ICP0 transcriptional activation. Fi- nally, the transcriptional inhibitory effect of VP22 on other viral promoters was demonstrated by the analysis of β-galactosidase activities in internal controls.

关键词： herpes simplex virus type 1 tegument VP22 transcriptional regulation

Adult black dot tinea capitis caused by Trichophyton tonsurans complicated with herpes zoster

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Chinese Medical Journal 2020年第1期133卷 91-93页

作者： Yu-Shi Zheng Xian-Yi Zhou Juan Luo Yong-Xuan Hu Kang-Xing Liu Zu-Hao Mao Zhong Wu Department of Dermatology The Third Affiliated Hospital of Southern Medical UniversityGuangzhouGuangdong 520010China Southem Medical University GuangzhouGuangdong 520010China

To the Editor:Tinea capitis(TC)is a common superficial fungal infection of the scalp,and the pathogens vary with geography and socioeconomic status.[1]We described a case of TC caused by Trichophyton tonsurans and sub... 详细信息

关键词： zoster superficial herpes

Fatal fulminant herpes simplex hepatitis following surgery in an adult

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World Journal of Clinical Cases 2018年第2期6卷 11-19页

作者： Yoshihiro Yokoi Takeshi Kaneko Tomoki Sawayanagi Yasuo Takano Yoichi Watahiki Department of Surgery Shinshiro Municipal Hospital Department of Pathology Shinshiro Municipal Hospital

We present a case of a healthy 72-year-old man with herpes simplex hepatitis (HSVH) development soon after ordinary surgery for biliary stones. A sudden onset of hepatitis associated with high fever and leukopenia emerged on postoperative day 5, followed by a rapid and lethal course (died on day 9), despite an acyclovir therapy on day 8. Postmortem liver biopsy revealed positive immunostaining for herpes simplex virus(HSV) type-1. The serum tests(available after the death) were negative for anti-HSV immunogloblulins, but positive for HSV DNA. A review of 15 cases of postsurgical HSVH along with 42 cases of non-surgical HSH showed that (1): A wide spectrum of surgical procedures was involved; and (2): High mortality (87%) associated with lower rates of ante-mortem diagnosis (20%) and acyclovir treatment (20%). Due to the difficulty in diagnosis and lethal nature, an early clinical suspension and prompt empirical anti-viral intervention are imperative for postsurgical hepatitis with undetermined etiology, characterized by fever and leucopenia.

关键词： herpes simplex virus Fulminant hepatitis Postsurgical Adult Acyclovir