What Exactly is MONKEYPOX Monkeypox is a rare disease that is caused by infection with monkeypox virus. Monkeypox virus belongs to the Orthopoxvirus genus in the family Poxviridae. The Orthopoxvirus genus also includes variola virus (the cause of smallpox), vaccinia virus (used in the smallpox vaccine), and cowpox virus. Monkeypox was first discovered in 1958