The Lab Notes

The main theme of our research is to understand how gene regulation and genome organization tie in with each other. The Lab Notes are the latest headlines from the lab, featuring a collection of random thoughts and useful code snippets.


The central theme of our latest article is to discuss the impact of the chromatin context on HIV latency. One of the most important findings was to show that HIV expression is a case of position effect: the viruses integrated close to endogenous enhancers have higher expression compared to those which integrates far from enhancers. Before this work, it was unclear whether the expression of HIV can be influenced by the location where it is inserted. The first article that studied this question was published by Albert Jordan. They found some heterogeneity in HIV expression from 34 Jurkat clonal cell lines, each containing a single integration. Consistently, we also found that HIV which integrates in different locations in a chromosome exhibits different levels of expression. Furthermore, we pointed out that latent HIV integrates slightly further from active endogenous enhancers compared to the active one.

Another key result of in this article is that latency-reversing agents have different effects towards different latent proviruses. The current strategy of antiretroviral therapies, called “shock and kill”, is to reactivate latent viruses so that infected cells containing activated HIV can be purged by the immune response. The first drug used in clinical...

The role of SWI/SNF in HIV-1 chromatin remodeling

If you type the keyword “SWI/SNF chromatin remodeling” and “HIV-1” in PubMed, less than 20 research articles appear on your screen. Actually, the topic of nucleosome remodeling of HIV-1 provirus is less than 10 years old. The more we investigate HIV-1, the more we know that the connection between host chromatin and HIV-1 pathogenesis cannot be ignored.

The integration of HIV-1 provirus into the cellular genome is an essential mechanism for the establishment of stable infection. After this step, how the HIV-1 provirus further manipulates chromosomal features to continue its life cycle is therefore considered important. SWI/SNF is one of the main actors involved in the alteration of DNA accessibility within repressive nucleosomes. In fact, back in 1996, the SWI/SNF regulator has been found in the RNA polymerase II holoenzyme and has been reported to be involved in chromatin remodeling [1]. Later, it was realized that the SWI/SNF complex found in both eukaryotes and prokaryotes is actually a group of proteins that associate to remodel the nucleosome state (active or repressive). SWI/SNF contains either Brahma (BRM) or the closely related BRG1 as its catalytic subunit and shares...

Silence is a weapon — HIV latency

I have been inspired to study virology by the movie Outbreak directed by Wolfgang Petersen in 1995. Since that time, I have been wondering how this tiny monster is so powerful as to bring disasters in our daily life. With this question always in the back of my mind, I walked into the world of microbes trying to reveal its mystery.

My current work in the laboratory is on the Human Immunodeficiency Virus type 1 (HIV-1), which causes Acquired Immuno-Deficiency Syndrome (AIDS). The phenomenon that most caught my attention is that HIV-1 is able to keep itself silent during the infection, which is called latency. Latent viruses are like a dormant volcano; they can be reactivated any time in favourable conditions. Therefore HIV-1-infected patients need to receive Highly Active Antiretroviral Therapy (HAART) with no interruption. Plasma virus rises within two to three weeks after discontinuation of HAART (from 20 to 50 RNA copies per mL, see Davey et al., 1999 for detail).

In order to be silent and invisible, HIV-1 needs secret places to hide and to make the infection persistent. Such special environments are called reservoirs, where viruses persist for longer...