Ectopic Expression of Human Herpesvirus 1 Thymidine Kinase Induces Male Infertility

Abstract

The herpesvirus family comprises several widespread infectious pathogens. They infect a variety of animal hosts, including humans and cause complex clinical outcomes. Recently, the possible correlation between genital infection by human herpesviruses HHVs and male infertility has attracted considerable attention. In this chaper, we investigated the mechanism of HHV--induced infertility in transgenic Tg rats and its possible correlation with infertility in human males. Ectopic expression of HHVthymidine kinase TK in the testis of Tg rats increased male infertility. In addition, truncated TK proteins were found in postmeiotic spermatids of Tg rat testis, leading to progressive degeneration of germ cells and vacuolization of the seminiferous epithelium. These findings suggest the possibility that a similar process occurs within HHVinfected human germ cells.Keywords: herpesvirus, thymidine kinase, genital infection, male infertility, spermatogenesis . IntroductionHerpesviruses belong to a family of double-stranded DN" dsDN" viruses commonly causing herpes in animals. They present a unique four-layered structure. The outermost layer corresponds to the envelope, a lipid bilayer membrane interspersed with glycoproteins. This encases the tegument, a protein coat that surrounds the icosahedral nucleocapsid containing the viral linear DN" genome Figure [ ]. "t present, over herpesvirus species have been identified, eight of which are known as human herpesviruses HHVs HHV-and HHVcommonly called herpes simplex virus-and -HSV-and HSV-, HHV-varicella-© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.zoster virus VZV , HHV-Epstein-"arr virus E"V , HHV-cytomegalovirus CMV , HHVhuman herpesvirus , including HHV-" and HHV-" , HHV-human herpesvirus , and HHV-Kaposi's sarcoma-associated herpesvirus KSHV . HHVs are divided into three subfamilies -, -and -herpesviruses based on their unique properties Table [ ]. HHVs are widespread among humans to the extent that more than % of adults are thought to be infected with at least one variety [ ]. HHVs generally infect ectoderm-derived tissues, such as skin, mucoepithelial tissue and nervous tissue however, they usually show preference for specific target cells/tissues and ensuing clinical outcomes Table [ ]. In addition, many people carrying the virus may be asymptomatic due to the latency of associated transcripts, which help HHVs evade the host's immune response [ ]. Moreover, HHVs hide in specific cells during latent infection periods Table . Figure . HHVs structure. HHVs have a unique four-layered structure a core of double-stranded DN" is surrounded by the nucleocapsid, which is enclosed by the envelope. The envelope is attached to the capsid through the tegument. Glycoproteins cover the surface of the envelope.During the last decade...