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Human endogenous retroviruses, hormones and APOBEC3G: A connection to explore in schizophrenia
Authors:Ignacio Iturrieta-Zuazo,Raú  l Alelú  -Paz
Affiliation:a Departamento de Anatomía, Histología y Neurociencia, Facultad de Medicina, Universidad Autónoma de Madrid, C/Arzobispo Morcillo s/n, 28029 Madrid, Spain
b Departamento de Psicobiología, Facultad de Psicología, Universidad Complutense de Madrid, Campus de Somosaguas, 28223 Madrid, Spain
Abstract:
Human endogenous retroviruses (HERVs) represent the footprints of previous retroviral infections. They are integrated within the human germ line and constitute approximately 7% of our genome. They have the potential to harm, given their capacity to alter the cellular metabolism, and could be involved in various pathological processes such as systemic lupus erythematosus or multiple sclerosis. In this respect it has been found that the stimulation of HERVs genome expression was observed after a steroid hormone treatment, stating the first evidence that an enhanced expression of the HERVs genome by hormones may be involved in the etiology of breast cancer. There is now increasing evidence that HERVs may in fact be involved in the etiology of schizophrenia, a disorder characterized by heterogeneous presence of positive, negative and cognitive symptoms that affect all aspects of mental activity, with a first peak incidence for males and females in the decade 15-24 and a second peak at age 55-64 for females, both periods characterized by two moments of significant hormonal changes. In connection with genetic aspects, several studies suggest a linkage between chromosome 22 (22q) and schizophrenia, being different genes of this chromosomal region reported as candidate genes for association with the disorder. Likewise, in a closely region of these genes, on 22q13, is located a gene named APOBEC3G, a potent intrinsic inhibitor of retroviral replication that also includes some HERVs. We propose that hormonal changes that coincide with two peak incidences in schizophrenia produce an enhancement in the expression of some HERV families implicated in the etiopathology of the disorder. The expression of HERVs is followed by a defective action of APOBEC3G that avoids carry out its function, that is, the inhibition of retroviral replication. This altered process might play a critical role in the etiopathogenesis of schizophrenia.
Keywords:Human endogenous retroviruses   Hormones   APOBEC3G   Schizophrenia
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