MORC3 restricts human cytomegalovirus infection by suppressing the major immediate-early promoter activity.

During the long coevolution of human cytomegalovirus (HCMV) and humans, the host has formed a defense system of multiple layers to eradicate the invader, and the virus has developed various strategies to evade host surveillance programs. The intrinsic immunity primarily orchestrated by promyelocytic leukemia (PML) nuclear bodies (PML-NBs) represents the first line of defense against HCMV infection. Here, we demonstrate that microrchidia family CW-type zinc finger 3 (MORC3), a PML-NBs component, is a restriction factor targeting HCMV infection. We show that depletion of MORC3 through knockdown by RNA interference or knockout by CRISPR-Cas9 augmented immediate-early protein 1 (IE1) gene expression and subsequent viral replication, and overexpressing MORC3 inhibited HCMV replication by suppressing IE1 gene expression. To relief the restriction, HCMV induces transient reduction of MORC3 protein level via the ubiquitin-proteasome pathway during the immediate-early to early stage. However, MORC3 transcription is upregulated, and the protein level recovers in the late stages. Further analyses with temporal-controlled MORC3 expression and the major immediate-early promoter (MIEP)-based reporters show that MORC3 suppresses MIEP activity and consequent IE1 expression with the assistance of PML. Taken together, our data reveal that HCMV enforces temporary loss of MORC3 to evade its repression against the initiation of immediate-early gene expression.

Correlations between fasciology and yin yang doctrine.

The aim of this study is to explore the correlations between fasciology and yin yang doctrine. Professor Yuan developed fasciology by three-dimensional reconstruction of connective tissue (fascia) in the trunk and limbs of the human body and tracing back to tissue origins in light of biological evolution and developmental biology. Fasciology states that the human body can be divided into two systems: the supporting-storing system and the functional system. This article elaborates on the roles of the two systems and their mutual relationship. The two systems are used to analyze the yin, the yang, and their relationship. The two systems are promoted but also restricted in different contexts. The supporting-storing system is formed by undifferentiated connective tissue and provides undifferentiated cells and nutrients for differentiated cells of the functional system. Thus, the supporting-storing system could be classified as quiet, similar to yin. The functional system continuously maintains the various functional activities of the human body. Thus, the functional system could be classified as active, similar to yang. In interpreting the yin yang doctrine from the point of view of fasciology, yin can be compared with the supporting-storing system and yang can be compared with the functional system.