# Utilizing Feline Lentiviral Infection to Establish a Translational Model for COVID-19 in People with Human Immunodeficiency Virus Infection

## TL;DR

Researchers used cats infected with a virus similar to HIV to study how SARS-CoV-2 behaves in immunocompromised hosts, finding that antiretroviral therapy helps reduce viral mutations.

## Contribution

A novel feline model is proposed to study coinfections of HIV-like and SARS-CoV-2 viruses, emphasizing the role of antiretroviral therapy.

## Key findings

- FIV+ cats untreated with AZT showed the poorest CD4+ T-cell response to SARS-CoV-2.
- FIV+ cats untreated with AZT exhibited persistent SARS-CoV-2 RNA in plasma and viral mutations.
- Antiretroviral therapy minimized SARS-CoV-2 mutations and improved immune response in coinfected cats.

## Abstract

People living with human immunodeficiency virus (PLWH) are a significant population globally. Research delineating our understanding of coinfections in PLWH is critical to care for those navigating infection with other pathogens. The recent COVID-19 pandemic underscored the urgent need for studying the effects of SARS-CoV-2 infections in therapy-controlled and uncontrolled immunodeficiency viral infections. This study established the utility of a feline model for the in vivo study of coinfections. Domestic cats are naturally infected with SARS-CoV-2 and Feline Immunodeficiency Virus, a lentivirus molecularly and pathogenically similar to HIV. In this study, comparisons are made between FIV-positive and FIV-negative cats inoculated with SARS-CoV-2 (B.1.617.2.) in an experimental setting. Of the FIV+ cats, three received Zidovudine (AZT) therapy in the weeks leading up to SARS-CoV-2 inoculation, and two did not. SARS-CoV-2 viral RNA was quantified, histopathologic comparisons of respiratory tissues were made, and T-cell populations were analyzed for immune phenotype shifts between groups. CD4+ T lymphocyte responses varied, with FIV+-untreated cats having the poorest CD4+ response to SARS-CoV-2 infection. While all cats had significant pulmonary inflammation, key histopathologic features of the disease differed between groups. Additionally, viral genomic analysis was performed, and results were analyzed for the presence of emerging, absent, amplified, or reduced mutations in SARS-CoV-2 viral RNA after passage through the feline model. Positive selection is noted, especially in FIV+ cats untreated with AZT, and mutations with potential relevance were identified; one FIV+-untreated cat had persistent, increasing SARS-CoV-2 RNA in plasma five days post-infection. These findings and others support the utility of the feline model for studying coinfection in people with HIV and highlight the importance of antiretroviral therapy in clearing SARS-CoV-2 coinfections to minimize transmission and emergence of mutations that may have deleterious effects.