The simultaneous presence and expression of human hepatitis C virus (HCV), human herpesvirus-6 (HHV-6), and human immunodeficiency virus-1 (HIV-1) in a single human T-cell.
We have developed a system that isolates and replicates HCV in vitro. These isolates are called CIMM-HCV. This system has made it possible to analyze the biology, nature, and extent of HCV variability, among other things. Individuals that are infected with HIV-1 are often also infected with HCV and HHV-6. In addition to HCV, our lab has systems for replicating HIV-1 and HHV-6. We asked whether all these viruses could infect the same cells. We report here the successful infection of a T-cell (CEM) by CIMM-HCV, HHV-6, and HIV-1. PCR analyses demonstrated that the CEM cells were productively infected by HHV-6A. RT-PCR showed that the same cell culture was positive for HCV and HIV-1. Co-infection of a T-cell by all three viruses was confirmed by transmission electron microscopy (TEM). All these viruses are highly cytolytic; therefore, triply-infected cells were short lived. However, HIV-1 and HCV co-infected cells unexpectedly lasted for several weeks. Viral replication was unhindered and the phenomenon of 'dominance' was not observed in our experiments. In addition, CIMM-HCV was present in the perinuclear space, suggesting their possible synthesis in the nucleus. This report is based entirely on viruses produced in vitro in our laboratories. As part of the determinations of host ranges of these viruses, studies were designed to demonstrate the infection of a single cell by these viruses and to study the consequences of this phenomenon. All measurements were made on cultured cells and cell culture supernatants.
Salahuddin
S Zaki
SZ
Department of Basic Research, California Institute of Molecular Medicine, Ventura, California, USA. zaki@cimm.net
Snyder
Katherine A
KA
Godwin
Andre
A
Grewal
Renu
R
Prichard
John G
JG
Kelley
Ann S
AS
Revie
Dennis
D
D018929:Cell Culture Techniques; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D015654:Herpesvirus 6, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D046529:Microscopy, Electron, Transmission; D013601:T-Lymphocytes / Q000648:ultrastructure / Q000821:virology*; D014771:Virion / Q000254:growth & development; D014779:Virus Replication / Q000235:genetics