Abstract:
Rift Valley fever phlebovirus (RVFV) infects humans and a wide range of ungulates and
historically has caused devastating epidemics in Africa and the Arabian Peninsula. Lesions of
naturally infected cases of Rift Valley fever (RVF) have only been described in detail in sheep with
a few reports concerning cattle and humans. The most frequently observed lesion in both ruminants and humans is randomly distributed necrosis, particularly in the liver. Lesions supportive
of vascular endothelial injury are also present and include mild hydropericardium, hydrothorax
and ascites; marked pulmonary congestion and oedema; lymph node congestion and oedema; and
haemorrhages in many tissues. Although a complete understanding of RVF pathogenesis is still
lacking, antigen-presenting cells in the skin are likely the early targets of the virus. Following suppression of type I IFN production and necrosis of dermal cells, RVFV spreads systemically, resulting
in infection and necrosis of other cells in a variety of organs. Failure of both the innate and adaptive
immune responses to control infection is exacerbated by apoptosis of lymphocytes. An excessive proinflammatory cytokine and chemokine response leads to microcirculatory dysfunction. Additionally,
impairment of the coagulation system results in widespread haemorrhages. Fatal outcomes result
from multiorgan failure, oedema in many organs (including the lungs and brain), hypotension, and
circulatory shock. Here, we summarize current understanding of RVF cellular tropism as informed
by lesions caused by natural infections. We specifically examine how extant knowledge informs
current understanding regarding pathogenesis of the haemorrhagic fever form of RVF, identifying
opportunities for future research.
