Viruses tipping the scales: The role of the CD4/CD8 ratio in determining viral outcome

• Published in: Virology (New York, N.Y.) N.Y.), 2025-02, Vol.603, p.110333, Article 110333
• Main Authors: Miller, Jacqueline Rose, Feng, Cynthia, Ranum, Jordan, Striker, Rob
• Format: Article
• Language: English
• ISSN: 0042-6822; 1096-0341; 1096-0341
• DOI: 10.1016/j.virol.2024.110333

Here we review recent data on how animal viruses alter the T cell dynamics, and how stressed T cell populations alter viral disease outcomes. The CD4/CD8 ratio of T cells is regulated by the thymus well into adulthood, and determined by both host genetics and environmental exposures. Human and animal data now show many chronic viral infections interact with this ratio and Immune Health Grades, but this raises new questions and justifies new experimental systems. Immune Health Grades and the ratio generally can quantify subtle immunodeficiency for viral infections. Whether or not an animal recovers from a viral infection, and how carcinogenisis proceeds for certain oncogenic viral infections can now be traced back to how “stressed that animal's immune system is as judged by a low CD4/CD8 ratio or elevated Immune Health Grade. We provide this review to encourage basic science virologists using animal models and veterinary virologists to further explore the interactions between the CD4/CD8 T cell ratio and viruses to improve both human and veterinary health. •When the thymus is healthy it maintains a higher number of CD4 T cells in the blood than CD8 T cells.•Low CD4/CD8 T cell ratios are associated with poor outcomes from many viruses including HIV, Covid-19 and Influenza.•Chronic viral infections including Cytomegalovirus, Hepatitis B Virus can lower CD4/CD8 T cell ratios. Low CD4/CD8 T cell ratios in People Living with HIV are associated with cancer, particularly anal and lung cancer.