Journal Article

Molecular analysis of lymphoid tissue from rhesus macaque rhadinovirus-infected monkeys identifies alterations in host genes associated with oncogenesis

Estep, Ryan Douglas, Li, He, Fei, Suzanne S., Manoharan, Minsha, Park, Byung S., Govindan, Aparna N., Wong, Scott W., Axthelm, Michael K.

2020

Overview

Rhesus macaque (RM) rhadinovirus (RRV) is a simian gamma-2 herpesvirus closely related to human Kaposi's sarcoma-associated herpesvirus (KSHV). RRV is associated with the development of diseases in simian immunodeficiency virus (SIV) co-infected RM that resemble KSHV-associated pathologies observed in HIV-infected humans, including B cell lymphoproliferative disorders (LPD) and lymphoma. Importantly, how de novo KSHV infection affects the expression of host genes in humans, and how these alterations in gene expression affect viral replication, latency, and disease is unknown. The utility of the RRV/RM infection model provides a novel approach to address these questions in vivo, and utilizing the RRV bacterial artificial chromosome (BAC) system, the effects of specific viral genes on host gene expression patterns can also be explored. To gain insight into the effects of RRV infection on global host gene expression patterns in vivo, and to simultaneously assess the contributions of the immune inhibitory viral CD200 (vCD200) molecule to host gene regulation, RNA-seq was performed on pre- and post-infection lymph node (LN) biopsy samples from RM infected with either BAC-derived WT (n = 4) or vCD200 mutant RRV (n = 4). A variety of genes were identified as being altered in LN tissue samples due to RRV infection, including cancer-associated genes activation-induced cytidine deaminase (AICDA), glypican-1 (GPC1), CX3C chemokine receptor 1 (CX3CR1), and Ras dexamethasone-induced 1 (RasD1). Further analyses also indicate that GPC1 may be associated with lymphomagenesis. Finally, comparison of infection groups identified the differential expression of host gene thioredoxin interacting protein (TXNIP), suggesting a possible mechanism by which vCD200 negatively affects RRV viral loads in vivo.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Activation-induced cytidine deaminase / Analysis / Animal welfare / Animals / Artificial chromosomes / B cells / Bacterial artificial chromosomes / Biochemistry / Bioinformatics / Biology and Life Sciences / Biopsy / Carcinogenesis / CD200 antigen / Cell Transformation, Neoplastic - genetics / Chemokines / Chromosomes / CX3C Chemokine Receptor 1 - genetics / CX3CR1 protein / Cytidine deaminase / Cytidine Deaminase - genetics / Development and progression / Dexamethasone / Disease / Diseases / Gene expression / Gene Expression Profiling - veterinary / Gene Expression Regulation, Neoplastic / Gene regulation / Gene therapy / Genes / Genetic aspects / Genetic regulation / Genetic research / Glucocorticoids / Glypicans - genetics / Health aspects / Heparan sulfate proteoglycans / Herpesviridae Infections - genetics / Herpesviridae Infections - veterinary / HIV / HIV patients / Human immunodeficiency virus / Immunology / Immunoproliferative diseases / Infection / Infections / Laboratory animals / Latency / Lymph nodes / Lymphocytes / Lymphoid tissue / Lymphoid Tissue - metabolism / Lymphoma / Lymphomas / Macaca mulatta / Medicine and Health Sciences / Monkeys / Monkeys & apes / Mutants / Non-Hodgkin's lymphomas / Pathogenesis / ras Proteins - genetics / Research and analysis methods / Rhadinovirus - pathogenicity / Ribonucleic acid / RNA / Sarcoma / Sequence Analysis, RNA - veterinary / Simian immunodeficiency virus / Thioredoxin / Thioredoxins / Tissue analysis / Transcription activation / Tumor Virus Infections - genetics / Tumor Virus Infections - veterinary / Tumorigenesis / Tumors / Vaccines / Virus Latency / Virus Replication / Viruses