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 time than they do in other cell types, thereby sustaining the infection. As far as we know, the main HIV-1 reservoirs include resting CD4+ T cells, macrophages, the central nervous system and gut-associated lymphocytes.

Not all the HIV-1 infected cells go to the stage of latency. For instance, 0.01% of the resting CD4+ T isolated from blood of HIV-1-infected individuals contain HIV-1 DNA (reviewed by Pierson et al., 2000). However, similarly to the Butterfly Effect, a tiny cause will have a huge consequence. Just because of this 0.01% undetected silent HIV-1 hiding in the reservoirs, as of today, we still do not have any approach to efficiently purge the infected cells of the patients.

Silence is a kind of behavior. The chinese phrase “沈默是金”, which means “silence is gold” explains that silence is a wisdom to face the world based on traditional Chinese philosophy. The same is true about latent HIV-1, it uses silence as a weapon to attack us. How to defend ourselves from viral attacks has become one of the most urgent issues that we have to face as humans.

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