M. Mayne et al., Gene expression profile of herpesvirus-infected T cells obtained using immunomicroarrays: Induction of proinflammatory mechanisms, J VIROLOGY, 75(23), 2001, pp. 11641-11650
Herpesvirus infections can frequently lead to acute inflammation, yet the m
echanisms regulating this event remain poorly understood. In order to deter
mine some of the immunological mechanisms regulated by human herpesvirus in
fections, we studied the gene expression profile of lymphocytes infected wi
th human herpesvirus 6 (HHV-6) by using a novel immunomicroarray. Our nylon
-based immunomicroarray contained more than 1,150 immune response-related g
enes and was highly consistent between experiments. Experimentally, we foun
d that independently of the HHV-6 strain used to infect T cells, multiple p
roinflammatory genes were increased and anti-inflammatory genes were decrea
sed at the mRNA and protein levels. HHV-6 strains A and B increased express
ion of the genes for interleukin-18 (IL-18), the IL-2 receptor, members of
the tumor necrosis factor alpha superfamily receptors, mitogen-activated pr
otein kinase, and Janus kinase signaling proteins. As reported previously,
CD4 protein levels were also increased significantly. Specific type 2 cytok
ines, including IL-10, its receptor, and IL-14, were downregulated by HHV-6
infection and, interestingly, amyloid precursor proteins and type 1 and 2
presenilins. Thus, T cells respond to HHV-6 infection by inducing a type I
immune response that may play a significant role in the development and pro
gression of diseases associated with HHV-6, including pediatric, hematologi
c, transplant, and neurologic disorders.