The HIV-1 Capsid: More than Just a Delivery Package

Abstract

Productive HIV infection requires integration of viral genes into the host genome. But how viral DNA gets to the nucleus in the first place remains one of the most controversial yet deceptively simple questions in HIV post-entry biology. This is illustrated in cartoons of viral entry, which often depict the entry process as an ‘explosion’ of the HIV capsid in the cytosol and independent movement of viral DNA through nuclear pores and into the nucleus. HIV enters the cell cytosol with two encapsidated RNA strands and must undergo reverse transcription (RT) to synthesise DNA. Even here there is no consensus for where, when or how RT happens. HIV must get into the nucleus, which in a non-dividing cell requires transport through the nuclear pore. Finally, the virus must ‘uncoat’: shed its protein capsid to allow its DNA to be spliced with that of the host. Where the virus uncoats and whether this is a single or multi-step process are similarly hotly debated. Understanding these processes is further complicated by three broad factors. First, that there are inter-relationships between these processes that may ensure HIV undergoes the right step at the right place at the right time. Second, the host has cofactors which the virus is dependent upon and must recruit but also immune factors that can sense and inhibit virus and so must be avoided. Third, HIV post-entry biology is cell-type dependent—meaning that factors which are essential in one cell type can be redundant in another.