Friend Retro virus studies reveal complex interactions between Intrinsic, Innate and Adaptive immunity

A broad class of RNA viruses with an envelope makes up retroviruses. It is a member of the Retroviridae family, which is characterized by the presence of ribonucleic acid in its genetic material and deoxyribonucleic acid in the genetic material of its hosts.

Friend Virus [FV] is a genus of Gammaretrovirus that belongs to the Orthoretroviridae subclass of Retrovirus. When injected into adult mice, it was determined to produce fatal leukemia, which was the initial finding made by Charlotte Friend at the Cancer Research Institute at Atlantic. FV is a retroviral complex made up of two viruses: spleen-focusing virus (SFFV), a replication-defective yet deadly component, and murine leukemia friend virus (FMuLV), a replication-competent helper virus that is not harmful to adult mice. Intrinsic, innate, and adaptive immunity's very complicated anti-retroviral mechanisms were discovered through experiments employing the FV virus mouse model.

The research on immune resistance to retroviral infections has benefited greatly from the use of FV. Among the most interesting advances in viral immunology have been the identification and characterization of the molecular basis of retroviral DNA detection by DNA sensors IFI16 and cGAS. The Friend Virus uses several PRRs [Pattern Recognition Receptors] to specifically elicit a range of intrinsic immune responses.

The induction of IFN 1 [Type 1 Interferon] is the first host response generated after different viral infections. During an acute FV infection, splenocytes generate more IFNalpha1 and IFNalpha6 subtypes. Thus, the suppression of acute FV replication is caused by the administration of IFN alpha. These proteins are called APOBEC3 (A3) deoxycytidine deaminases. When integrated into FV cells, the mA3 gene generated by an infected cell suppresses the replication in the subsequent target cell. This guarantees the B cells will develop antibodies directed against it. Tetherin/BST2, a 28–36 kDa protein, functions as an immunomodulator in cell-mediated immunity by preventing the release of virions in FV cells. One important component of innate immunity is the complement system. Murine retroviruses called F-MuLV adapt CD55 and CR1-related gene/protein/Y (Crry), a rodent-specific RCA. Through a variety of methods, these genes control the complement system, which prevents retroviral virolysis. In FV infection, the complement has two sides like a coin. On the one hand, the FV benefits from complement protein opsonization, which enhances the virus's dissemination and raises infection levels

However, complement functions as a natural adjuvant to trigger CD8+ T cell responses specific to FV, which is necessary to manage acute FV infection. Adaptive immunity is greatly aided by dendritic cells, CD4+ T cells, CD8+ T cells, and the B cell response.CD4+ T cells specific to FMuLV are vital for the management of FV infections.

Additionally, F-MuLV-reactive CD4+ T cells enhance cellular immunity. During a prolonged FV infection, they also develop cytotoxic activity against targets that express MHC II. This cytotoxic action is dependent on FasL, whereas in the natural FV infection, CD4+ Tregs appear to block granzyme-dependent cytotoxicity, which can arise in response to F-MuLVenv124–138 vaccination administered by heterologous viral vectors. It has been demonstrated that during FV infection, Tregs are highly activated, proliferate, and inhibit all functional subsets of effector CD4+ and CD8+ T cells specific to FV throughout both the acute and chronic stages of infection. It was demonstrated in 1963 that animals infected with FV had antibody responses against both FV virions and FV leukemia cells.

Studies demonstrating the potential protective effect of passive antibody transfers of FV-specific antibodies against FV-induced leukemia have highlighted the significance of these antibodies. The FV model has been widely employed in recent decades to develop and evaluate innovative immunotherapy ideas against infectious illnesses. The FV model offers the chance to research immunotherapeutics that improve viral immunity both during an established chronic viral infection and during an acute illness.