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.

B-HIVE

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...






HIV Therapies – From “Hit Hard, Hit Early” to “Shock and Kill”

Since the outbreak of AIDS more than 30 years ago in the United States, HIV/AIDS is still one of the top ten causes of death worldwide [1]. One of the difficulties to cure HIV/AIDS is due to the lack of an effective HIV vaccine, although numerous laboratories are searching for it.

In 1995, David Ho first promoted a “hit hard, hit early” approach to eliminate HIV-1 infection in the early phase of the infection [2]. Yet, later on this approach was abandoned because of the high risk of side effects and the high cost of the treatment, this approach is still a milestone in the history of HIV/AIDS treatment. Nowadays, the standard approach for HIV/AIDS treatment is based on the standard antiretroviral therapy (ART) combining at least three antiretroviral (ARV) drugs to maximally suppress the HIV virus and stop the progression of HIV disease. Typical combinations include 2 nucleoside Reverse Transcriptase Inhibitors (NRTIs) + 1 Protease Inhibitor (PI) or 2 NRTIs + 1 non-nucleoside Reverse Transcriptase Inhibitor (NNRTI) [3]. Clinical studies showed that ART is able to impressively decrease the mortality of AIDS patients.

It was gradually realized that one of the main reasons...






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...