CD4 and Flavivirus Infections: However, although a study on human flaviviruses showed that the virus can infect CD4+ T lymphocytes and lead to reduced CD4 expression in infected patients (Xiang et al., 2009), the generation of virus-specific CD4+ T lymphocytes remains critical for achieving protective, long-lasting immunity against natural flavivirus infections (Aberle et al., 2018; Li et al., 2018).