Influence of interferon on virus‐particle synthesis in oncornavirus‐carrier lines. II. Evidence for A direct effect on particle release

Abstract

Interferon treatment of murine C‐type oncornavirus carrier lines results in a drastic inhibition of extracellular virus formation. When such cells are subcultured in the presence of interferon, synthesis of extracellular C‐type virus remains depressed until the interferon treatement is discontinued. Cell‐associated virus as seen in the electron microscope or as detected by uridine incorporation is not proportionally inhibited. Several possibilities to explain this discrepancy are tested. The most likely hypothesis is that interferon treatment primarily inhibits virus release.

Reduced synthesis of pp60src and expression of the transformation-related phenotype in interferon-treated Rous sarcoma virus-transformed rat cells.

“…These results are surprising in view of previous studies, which have shown that IFN treatment of murine cells exogenously or endogenously infected by murine leukemia virus does not affect either the transcription of the viral genome or the synthesis of viral proteins, although virus release is inhibited (5,6,16,37 (28). Thus, the effect of IFN treatment on the expression of pp6..src in RSV-transformed rat cells appears to be analogous to its effects on the expression of certain normal cellular genes.…”

In Vitro Treatment of Human Monocytes/Macrophages with Myristoylated Recombinant Nef of Human Immunodeficiency Virus Type 1 Leads to the Activation of Mitogen-Activated Protein Kinases, IκB Kinases, and Interferon Regulatory Factor 3 and to the Release of Beta Interferon

“…A possible explanation could be found in the capability of type I IFNs to protect the macrophages from a productive infection, as reported in early publications (9,61,77), leading to the establishment of a persistent infection and to the creation of a viral reservoir in a cell type that is particularly resistant to antiretroviral therapies (28). In fact, it is well known that type I IFNs inhibit the release of viral particles in cells chronically infected by retroviruses in the absence of a significant reduction of viral macromolecular synthesis (9,15,22,23,38,69,72,77,89) and that antiserum to type I IFNs can increase retrovirus production by a factor of 10 to 50 (12). In this respect, it is also interesting to remember that in the early 1980s, one of the first clear-cut HIV isolates was obtained from cultured T lymphocytes derived from a lymphonode biopsy specimen from a patient with lymphadenopathy, with the help of IL-2 and anti-IFN-␣ serum (11).…”

“…Real-time PCR assays were performed on total RNA isolated from MDMs treated or not for 2 h with 100 ng/ml of recombinant Nef or its mutants, using the RNeasy mini kit (QIAGEN, Milan, Italy) according to the manufacturer's instructions. Five hundred nanograms of total RNA was reverse transcribed using oligo(dT) [12][13][14][15][16][17][18] (Pharmacia-Biotech) as a primer and 50 units of Moloney murine leukemia virus reverse transcriptase enzyme (Gibco-BRL). Quantitative real-time PCR was then performed on reverse-transcribed IFN-␤ mRNA.…”

Interferon Enhances the Expression of Epstein--Barr Virus Early Antigen in Daudi Cells

“…To our knowledge, these results show for the first time that interferon can activate the genome of a latent human virus resulting in the production of virus-specified proteins. Although interferon has been shown to increase the intracellular concentration of the viral P30 group-specific antigen in ceils infected with endogenous murine leukaemia virus (Friedman & Ramseur, 1974;Billiau et al, 1974), the P30 antigen accumulates within the cell as a result of the inhibition by interferon of a late stage in virus assembly and/or release (Friedman, 1979) and may not be comparable to the activation of latent EBV.…”