Prior Puma Lentivirus Infection Modifies Early Immune Responses and Attenuates Feline Immunodeficiency Virus Infection in Cats.

Wendy Sprague,Ryan Troyer,Susan Vandewoude,Britta Wood,Scott Carver,Martha Macmillan,Xin Zheng

doi:10.3390/v10040210

Abstract

We previously showed that cats that were infected with non-pathogenic Puma lentivirus (PLV) and then infected with pathogenic feline immunodeficiency virus (FIV) (co-infection with the host adapted/pathogenic virus) had delayed FIV proviral and RNA viral loads in blood, with viral set-points that were lower than cats infected solely with FIV. This difference was associated with global CD4+ T cell preservation, greater interferon gamma (IFN-γ) mRNA expression, and no cytotoxic T lymphocyte responses in co-infected cats relative to cats with a single FIV infection. In this study, we reinforced previous observations that prior exposure to an apathogenic lentivirus infection can diminish the effects of acute infection with a second, more virulent, viral exposure. In addition, we investigated whether the viral load differences that were observed between PLV/FIV and FIV infected cats were associated with different immunocyte phenotypes and cytokines. We found that the immune landscape at the time of FIV infection influences the infection outcome. The novel findings in this study advance our knowledge about early immune correlates and documents an immune state that is associated with PLV/FIV co-infection that has positive outcomes for lentiviral diseases.

Highlights

Feline immunodeficiency virus (FIV) infection, which is a pathogenic lentivirus of domestic cats, causes fatal immune dysfunction that is characterized by progressive depletion of CD4+ T lymphocytes that is similar to HIV infection of humans [1,2]
We found that cats that were infected with non-pathogenic Puma lentivirus (PLV) and infected with pathogenic feline immunodeficiency virus (FIV) had delayed FIV proviral and RNA viral load detection in blood, with an overall viral set-point decrease compared to cats
We documented that prior exposure to apathogenic PLV infection resulted in the preservation of CD4+ T cells and increased Peripheral blood mononuclear (PBMC) IFN-γ mRNA expression when compared with cats that were infected solely with FIV [7]

Summary

Introduction

Feline immunodeficiency virus (FIV) infection, which is a pathogenic lentivirus of domestic cats, causes fatal immune dysfunction that is characterized by progressive depletion of CD4+ T lymphocytes that is similar to HIV infection of humans [1,2]. Viruses 2018, 10, 210 infected solely with FIV This difference was associated with global CD4+ T cell preservation and greater interferon gamma (IFN-γ) mRNA expression, but not cytotoxic T lymphocyte responses in co-infected cats relative to cats with single FIV infection [7,8]. PLV or single FIV infection [9], and multivariate analysis implicates immediate anti-PLV immune responses involving CD8+ T cells, CD25+ cells, IL-4, IFN-γ, and the death receptor (FAS) as correlates of attenuated disease in co-infected cats [10]. The current study aimed to compare lymphocyte and cytokine responses in blood, bone marrow, and lymphoid tissues of cats that were acutely infected with a pathogenic FIV isolate vs. those acutely that were infected with a nonpathogenic PLV isolate, followed by co-infection with pathogenic FIV

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