Hantaan virus is the causative agent of hemorrhagic fever with renal syndrome (HFRS). The Hantaan virus strain, Korean hemorrhagic fever virus clone-5 (KHF5), causes weight loss and renal hemorrhage in laboratory mice. Clone-4 (KHF4), which has a single E417K amino acid change in its glycoprotein, is an avirulent variant. In this study, KHF4 and KHF5 were compared to evaluate pathological differences in mice in vitro and in vivo. The characteristics of the two glycoproteins were not significantly different in vitro. However, the virulent KHF5 strain targeted the lungs and caused pneumonia and edema in vivo. Both strains induced high infectivity levels in the liver and caused hepatitis; however, petechial hemorrhage and glycogen storage reduction were observed in KHF5-infected mice alone. Renal hemorrhage was observed using viral antigens in the tubular region of KHF5-infected mice. In addition, an increase in white blood cell levels and neutrophilia were found in KHF5-infected mice. Microarray analysis of liver cells showed that CD8+ T cell activation, acute-phase protein production, and neutrophil activation was induced by KHF5 infection. KHF5 infectivity was significantly increased in vivo and the histological and clinicopathological findings were similar to those in patients with HFRS.

Hantavirus research in Africa has expanded from isolated serological observations to molecular detection of viruses in rodent, shrew, and bat hosts. This concise narrative review summarizes evidence for human serological exposure, host-associated virus diversity, genomic characterization, and public-health relevance. Human serological evidence compatible with hantavirus exposure has been reported in Guinea, Côte d’Ivoire, Gabon, the Democratic Republic of Congo, Madagascar, Mozambique, and Uganda. The strongest African human evidence consists of serological findings compatible with exposure: Sangassou-virus-compatible antibodies in febrile Guinean patients and Bowé-virus-specific IgM in a Côte d’Ivoire patient with fever and renal failure; however, viral RNA has not been recovered from an African patient specimen. Molecular studies have identified Sangassou virus in African wood mice, Seoul orthohantavirus in Senegalese black rats, and diverse shrew- and bat-associated lineages across West, Central, and East Africa. These findings demonstrate substantial viral diversity and human exposure, but do not establish that most newly detected viruses cause human disease. The 2026 Andes orthohantavirus outbreak associated with the cruise ship Hondius—13 cases and three deaths—illustrates the importance of imported-infection preparedness rather than African transmission. Africa’s central research gap is the absence of integrated surveillance linking unexplained febrile illness, validated serology, molecular confirmation, host sampling, and complete viral genomes.