Receptor usage and pathogenesis in acute and chronic viral infection

In the first phase of the viral life cycle, the virus enters cells using a specific cell surface receptor. Many viruses use multiple receptors: some of which are unique to a certain cell type, while others are ubiquitous in many cell types. Depending on the receptors used, the viral cell tropism is determined, which may result in the characteristic distribution of virus- infected cells/tissues. Obviously, virus entry is not the whole story. After the virus enters, various cellular proteins interact with it – some support virus replication, while others inhibit it. The intrinsic anti-viral cellular machinery differs among cell types; thus, viral cell tropism based on the receptor usage plays an important role in the pathogenesis. For example, HIV-1 utilizes one of two co-receptors, CXCR4 or CCR5, in addition to a major receptor, CD4. CCR5 expression is restricted to a certain subset of memory CD4+T cells, while CXCR4 expression is rather ubiquitous among CD4+T cells. Therefore, the latent infection of CCR5-utilizing HIV-1 in resting memory (CCR5+) T cells would be largely responsible for intermittent virus blimps accompanied by immune activation during chronic HIV infection. This may explain why CCR5-utilizing HIV-1 is preferentially isolated in the early phase of HIV-1 infection, even when the HIV-1 transmitter carries CXCR4-utilizing HIV-1 in abundance. In the case of the measles virus, CD150 (Signaling Lymphocyte Activation Molecule: SLAM) is a major receptor, while vaccine strains utilize CD46 when CD150 is not available. The third possible entry receptor would also be utilized for the infection of lung epithelial cells. The impact of these receptor usages in vivo on the disease outcome is now under investigation. We also know that the distinct use of host cell sugar moieties mediates species tropism in the influenza virus, and that a mutant virus breaking the species barrier is highly pathogenic in humans.

Thanks to the recent development of reverse genetics, it is now possible to visualize virus-infected cells, or even the virus itself, by using highly sensitive flow cytometery or microscopy. How viral cell tropism, determined by the receptor used, can affect the disease course of acute and chronic virus infection is an important question to address. In this Research Topic, we focus on studies connecting virus receptor usage and the pathogenesis of various viruses causing acute or chronic infection.