title: Prior virus exposure alters the long-term landscape of viral replication during feline lentiviral infection.
abstract: We developed a feline model of lentiviral cross-species transmission using a puma lentivirus (PLV or FIV(Pco)) which infects domestic cats but does not cause disease. Infection with PLV protects cats from CD4+ T-cell decline caused by subsequent infection with virulent feline immunodeficiency virus (FIV). Previous studies implicate innate immune and/or cellular restriction mechanisms for FIV disease attenuation in PLV-infected cats. In this study, we evaluated viral infection and cytokine mRNA transcription in 12 different tissue reservoirs approximately five months post infection. We quantitated tissue proviral load, viral mRNA load and relative transcription of IL-10, IL-12p40 and IFNγ from tissues of cats exposed to FIV, PLV or both viruses and analyzed these parameters using a multivariate statistical approach. The distribution and intensity of FIV infection and IFNγ transcription differed between single and co-infected cats, characterized by higher FIV proviral loads and IFNγ expression in co-infected cat tissues. Variability in FIV mRNA load and IFNγ was significantly more constrained in co-infected versus singly infected cat tissues. Single-infected:co-infected ratios of FIV mRNA load compared to FIV proviral load indicated that active viral transcription was apparently inhibited during co-infection. These results indicate that previous PLV infection increases activation of tissue innate immunity and constrains the ability of FIV to productively infect tissue reservoirs of infection for months, independent of FIV proviral load, supporting a model in which innate immunity and/or modulation of target cell susceptibility play a key role in PLV-induced protection from FIV disease.
authors: Department of Microbiology, Immunology and Pathology, 1619 Campus Delivery, Colorado State University, Fort Collins, CO 80523, USA. xin.zheng@colostate.edu
authors: Xin
authors: X
authors: Zheng
authors: Scott
authors: S
authors: Carver
authors: Ryan M
authors: RM
authors: Troyer
authors: Julie A
authors: JA
authors: Terwee
authors: Sue
authors: S
authors: VandeWoude
mesh_terms: D000818:Animals; D000829:Animals, Domestic; D000914:Antibodies, Viral / Q000097:blood*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002371:Cat Diseases / Q000276:immunology* / Q000635:transmission / Q000821:virology; D002415:Cats; D060085:Coinfection; D056738:Cross Protection; D007113:Immunity, Innate; D016089:Immunodeficiency Virus, Feline / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D053762:Interleukin-12 Subunit p40 / Q000235:genetics; D016180:Lentivirus Infections / Q000276:immunology / Q000635:transmission / Q000662:veterinary* / Q000821:virology; D015999:Multivariate Analysis; D046011:Puma / Q000821:virology*; D012333:RNA, Messenger / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D019562:Viral Load; D014779:Virus Replication / Q000502:physiology
chemical_list: D000914:Antibodies, Viral; D053762:Interleukin-12 Subunit p40; D012333:RNA, Messenger; D012367:RNA, Viral; D016753:Interleukin-10; D007371:Interferon-gamma