Infection of B Cell Follicle-Resident Cells by Friend Retrovirus Occurs during Acute Infection and Is Maintained during Viral Persistence

Abstract

Human immunodeficiency virus is notorious for its ability to avoid clearance by therapeutic interventions, which is partly attributed to the establishment of reservoirs in latently infected cells and cells that reside in immunologically privileged B cell follicles. In the work presented here, we show that cells of the B cell follicle are equally infected by a simple mouse gammaretrovirus. Using fluorescently labeled Friend retrovirus, we found that B cells and T cells in the B cell follicle, while not carrying the bulk of the virus load, were indeed infected by Friend virus in the early acute phase of the infection and persisted in the chronic infection. Our results suggest that infection of follicular cells may be a shared property of lymphotropic viruses and propose the FV infection of mice as a useful model to study strategies for follicular reservoir elimination.

Immunization with a murine cytomegalovirus based vector encoding retrovirus envelope confers strong protection from Friend retrovirus challenge infection

“…Again, about half of the Env-specific CD4 + T cells expressed CXCR5 in MCMV.env immunized as well as in unvaccinated mice. The frequency of Env-specific CD4 + T cells after FV infection was lowest in lymph nodes, which carry only relatively low viral loads in FV infection [16].…”

“…FV is regarded as a useful retrovirus mouse model that allows for insights into immunological control of retrovirus infections in general, and it shows similarities to HIV infection with regard to the establishment of persistent reservoirs in immunologically privileged sites [16] as well as immunosuppression driven by regulatory T cells [17, 18]. As low doses of FV are sufficient to rapidly induce disease in susceptible mice, FV infection is a very stringent mouse model for the development and evaluation of immunization strategies.…”

Fcγ Receptor Type I (CD64)-Mediated Impairment of the Capacity of Dendritic Cells to Activate Specific CD8 T Cells by IgG-opsonized Friend Virus

“…The generation of a recombinant F-MuLV encoding the bright fluorescent protein mWasabi (wF-MuLV) has been described previously [ 28 ]. Briefly, the green fluorescent protein mWasabi [ 29 ] was fused to the C-terminus of the F-MuLV envelope, using the 2A self-cleaving peptide of porcine teschovirus for the joining of the sequences [ 30 ] ( Figure S1, Supplementary Materials ).…”

Friend retrovirus studies reveal complex interactions between intrinsic, innate and adaptive immunity

“…In fact, mice with the long form of Stk (LF-Stk), which does not interact with gp55, are highly resistant to FVinduced splenomegaly and disease (Table 1). FV also infects B cells and myeloid cells, whereas infection levels of T cells are much lower (Windmann et al 2019). In resistant mice, infected erythroid precursors are efficiently eliminated by T cells, but the infected immune cell populations can partly escape from T cell Downloaded from https://academic.oup.com/femsre/article-abstract/43/5/435/5489187 by guest on 09 June 2020 killing.…”

“…In resistant mice, infected erythroid precursors are efficiently eliminated by T cells, but the infected immune cell populations can partly escape from T cell Downloaded from https://academic.oup.com/femsre/article-abstract/43/5/435/5489187 by guest on 09 June 2020 killing. Infected T and B cells subsequently accumulate in B cell follicles (Windmann et al 2019), a specific immunological niche that cytotoxic cells usually can't excess and that also harbors the viral reservoir in HIV infected humans or SIV infected monkeys (Connick et al 2014;Fukazawa et al 2015).…”