According to the report released by WHO, HIV is still a great threat to the health of human beings around the world. HIV infection will destroy the immune system of the infected persons, leading to the immune deficiency symptom, namely, Acquired Immune Deficiency Syndrome (AIDS). Due to the malfunction of the immune system, AIDS patients will be more easily subjected to the infection of internal and external pathogenic microorganisms. Without the intervention of drugs, they will die of pathogenic micro-organic infection. Up to 2014, there were about 36.9 million HIV carriers. Within 2014, there are over one million patients died of AIDS. At present, there are several anti-viral drugs for relieving the diseases, each of which is used for inhibiting a certain stage in the virus life cycles. The joint use of several drugs is the common therapy strategy now, which is the so-called highly active antiretroviral therapy (HAART). By effectively controlling the replication of virus, this strategy can slow down the development of symptoms. However, without the function of eliminating the virus genomic DNA infected into the cells, these drugs can not cure AIDS. In addition, the complicated life cycle of viruses and their latencies bring great challenges to research and treatment. It remains urgent and necessary to study the molecular mechanisms of HIV in the replication of host cells, which might lay a solid reference and testing foundation for the development of new drugs.
Guangxia GAO’s team from IBP, CAS, has been devoted to studying the interaction between HIV and host-cell proteins. They have carried out the thorough and systematic research on the mechanism of the inhibition of Zinc-Finger Antiviral Protein (ZAP) on HIV replication, and have found that ZAP inhibits viral infection through promoting target viral mRNA degradation. The ZAP-mediated target mRNA degradation is caused by specifically binding to viral mRNA elements to induce translation repression. ZAP also recruits host RNA-decay factors to facilitate the degradation of target RNA.
In a new study published by Cell Host & Microbe on 23rd July, 2015, titled HIV Exploits the Host Factor RuvB-like 2 to Balance Viral Protein Expression, Guangxia Gao’s group released the interesting findings of the interaction between HIV and host cells. They find RuvB-like 2 (RVB2) inhibits Gag expression. By Interacting with both the 5’ untranslated region of target mRNA and newly-translated proteins, RVB2 Induces ribosome pausing and realizes the inhibition of Gag protein expression. Interestingly, by competing with RVB2 to bind to Gag proteins, HIV encoded envelope protein can antagonize RVB2 from inhibiting Gag expression. According to more precise analysis, the expression amount of envelope proteins is very low at the early stages of viral gene expression. Since Gag proteins can form viral particles by themselves, the produced viruses are free from infection without adequate envelope proteins. The amount of envelop proteins at this stage is unable to antagonize RVB2. With the help of endogenous RVB2, the number of viral particles reduces. Thus, the possibility of producing non-infected viruses without envelope proteins is decreased. As time goes by, the expression amount of envelope proteins in cells increases, which will meet the needs of virus production and be capable of antagonizing RVB2, following that Gag expression will not be inhibited by RVB2. Thus, viruses production can go on smoothly. By making use of one inhibitory factor of host cells, HIV replicates effectively and reduces the risk of being attacked by immune system due to producing too much non-infected particles. Prof. Hong SHANG’s group, their collaborator, from the First Affiliated Hospital, China Medical University in Shenyang, found the positive correlation between RVB2 expression level and pathogenic progression of HIV, which provided strong proof for their findings.
Taking advantage of its own properties and the internal environment of host cells, these viruses replicate effectively and precisely, just like controlling an assembly line, whose quantity and quality are under monitoring and controlling. These findings extend our acknowledgement of HIV and broaden our horizon in the interaction between host and viruses. Guangxia GAO’s group will continue to explore in this area. The joint efforts of all research groups will bring a bright future for fighting against HIV.
