Simian hemorrhagic fever virus (SHFV) causes a fatal hemorrhagic
fever in macaques but an asymptomatic,
persistent infection in baboons. To investigate factors contributing to this differential
infection outcome, the targets of SHFV
infection, macrophages (MΦs) and myeloid dendritic cells (mDCs), were differentiated from macaque and baboon peripheral blood monocytes and used to compare viral replication and cell responses. SHFV replicated in >90% of macaque MΦs but in only ∼10% of baboon MΦs. Although SHFV infected ∼50% of macaque and baboon mDCs, virus replication was efficient in macaque but not in baboon mDCs. Both types of macaque cultures produced higher virus yields than baboon cultures. A more efficient
type I interferon response and the production of proinflammatory
cytokines, including interleukin-1β (IL-1β),
IL-6,
IL-12/23(p40),
tumor necrosis factor alpha (TNF-α), and
macrophage inflammatory protein 1α (MIP-1α), in response to SHFV
infection were observed in macaque but not baboon cultures, suggesting less efficient counteraction of these responses by
viral proteins in macaque cells. Baboon cultures produced higher levels of
IL-10 than macaque cultures both prior to and after SHFV
infection. In baboon but not macaque cell cultures, SHFV
infection upregulated IL-10R1, a subunit of the
IL-10 receptor (IL-10R), and also SOCS3, a negative regulator of proinflammatory
cytokine production. Incubation of macaque cultures with human
IL-10 before and/or after SHFV
infection decreased production of
IL-6, IL-1β, and MIP-1α but not TNF-α, suggesting a role for
IL-10 in suppressing SHFV-induced proinflammatory
cytokine production in macaques.