Characterization of a CD4-independent clinical HIV-1 that can efficiently infect human hepatocytes through chemokine (C-X-C motif) receptor 4

Abstract

The present study provides evidence that emergence of CD4-independent HIV-1 virus in vivo may occur in HIV-1-infected patients. In addition, these results shed light on the mechanisms involved in liver damage in HIV-1-infected individuals, which could have important implications concerning the range of mutability and the pathogenesis of AIDS.

Inefficient fusion due to a lack of attachment receptor/co-receptor restricts productive human immunodeficiency virus type 1 infection in human hepatoma Huh7.5 cells

“…Our results describing a very weak in vitro infection of human hepatoma cells may appear at odds with those previously reported in other studies (Banerjee et al, 1992;Cao et al, 1990;Iser et al, 2010;Xiao et al, 2008). For example, Banerjee and colleagues reported the presence of Fig.…”

“…The explanation for this discrepancy is currently unknown but could relate to a distinct cellular clone. A CD4-independent HIV-1 productive infection of primary human hepatocytes and established cell lines has been demonstrated previously (Banerjee et al, 1992;Cao et al, 1990;Iser et al, 2010;Xiao et al, 2008). However, it must be stated that some crucial controls were missing from the study by Cao and co-workers, such as inhibition of infection by HIV-1-specific inhibitors allowing discrimination between de novo particles production and recycling.…”

“…Our results suggest that intrinsic features of the HIV-1 Env are necessary to use GalCer as a receptor on the surface of hepatocytes since pseudotyping with NDK Env results in a superior virus gene expression in Huh7.5 cells. Recently, the CD4-independent clinical HIV-1 strain SDA-1 has been shown to infect with some efficiency primary human hepatocytes (Xiao et al, 2008). It would be interesting to know whether the SDA-1 Env uses the GalCer-mediated alternate pathway to infect primary human hepatocytes.…”

“…As for hepatocytes, the parenchymal cells of the liver, they constitute about two-thirds of the total cell population in this organ and are involved in many biological processes. Their susceptibility to HIV-1 is still controversial (Banerjee et al, 1992;Cao et al, 1990;Iser et al, 2010;Lin et al, 2008;Xiao et al, 2008). Nevertheless, two groups have clearly identified the presence of HIV-1 in hepatocytes in vivo (i.e.…”

Resolving the Sites of HIV Entry: Dynamin Networks Hold the Key

“…Differential chemokine usage can be leveraged to focus gene delivery into memory resting CD4 T cells if CCR5 using envelopes are used or across both memory and naïve T cells if CXCR-4 and dual tropic CCR5/CXCR-4 using envelopes are utilised. Finally and importantly, there is further precedent, both in vitro and in vivo, for HIV to directly bind and enter cells through chemokine receptors alone (CD4 independent), providing a potential platform wherein both CD4 and CD8 T cells can be targeted by CCR5/CXCR-4 alone [137][138][139][140]. One may even tune these CD4 independent HIV envelopes to target other chemokine receptors and in turn provide further gene targeting precision to cells within our immune system.…”