# The Giant Panda Transferrin Receptor Facilitates Feline Parvovirus Infection to Drive Cross-Species Transmission

## TL;DR

This study shows how feline parvovirus infects giant pandas by using their transferrin receptor, explaining the risk and offering insights for protecting pandas.

## Contribution

The study identifies the giant panda transferrin receptor as a key factor enabling feline parvovirus cross-species infection.

## Key findings

- Giant panda transferrin receptor 1 (gpTfR1) enhances feline parvovirus replication in non-susceptible cells.
- gpTfR1 facilitates viral attachment and internalization during early infection stages.
- The study provides the first evidence of FPV cross-species infection mechanisms in giant pandas.

## Abstract

Feline parvovirus (FPV) is a dangerous virus that causes severe illness in cats, including vomiting, diarrhea, and life-threatening infections. Recently, infection with this virus has also been reported in giant pandas, leading to similar symptoms and even death, putting these endangered animal species at risk. To understand how FPV spreads to pandas, we studied a panda-derived strain of the virus and examined how it interacts with panda host factors. The FPV virus uses a specific protein—namely the transferrin receptor 1—to enter and multiply inside cells. By testing this interaction in human cells that normally resist infection, we confirmed that the panda version of this receptor allows the virus to attach, enter, and replicate efficiently. These findings help explain why giant pandas are vulnerable to FPV and provide crucial insights for developing vaccines or treatments to protect them. Our research not only advances the understanding of cross-species virus transmission but also supports conservation efforts to safeguard giant pandas from deadly outbreaks.

Feline parvovirus (FPV) causes feline panleukopenia, a highly contagious disease in cats, marked by severe leukopenia, biphasic fever, diarrhea, vomiting, and hemorrhagic enteritis. Recently, FPV infection in giant pandas has increased, causing diarrhea and ultimately fatal outcomes, thereby threatening their survival and reproduction. Here, we investigated the transmission of FPV in giant pandas and its interaction with cellular receptors using an FPV strain (pFPV-sc) isolated from giant panda feces. Recombinant feline transferrin receptor 1 (fTfR1) and the giant panda ortholog (gpTfR1) were expressed in non-susceptible HEK293T and HeLa cells, while viral infection levels were measured to determine the effect of gpTfR1 on pFPV-sc replication. The findings indicated that gpTfR1 overexpression in non-susceptible cells significantly enhanced pFPV-sc replication, particularly influencing the viral attachment and internalization stages. Our data further revealed early-stage colocalization between gpTfR1 expression and virus infection, suggesting that gpTfR1 facilitates early viral infection and replication. Taken together, our study provides the first evidence on the mechanism of FPV cross-species infection in giant pandas and elucidates the interaction between gpTfR1 and FPV, which establishes a theoretical basis for the development of preventive and therapeutic strategies, thereby safeguarding the health and survival of giant panda populations from FPV.