Arch Virol (2004) 149: 2079–2093
Induction of MHC-I and thymic depletion due to replication
of JEV in mouse brain
Y. Kavitha and R. Manjunath
Department of Biochemistry, Indian Institute of Science, Bangalore, India
Received July 24, 2003; accepted May 28, 2004
Published online July 23, 2004
Summary. The thymus is a primary lymphoid organ that is responsible for T
cell development and maturation.Thymic depletion accompanied by apoptosis and
altered T cell maturation occurs during several viral infections. Here we show that
adult mice intracerebrally infected with Japanese encephalitis virus exhibit severe
cell depletion and alterations in the CD4
single as well as CD4
double positive cell populations. A 5.6 fold induction of MHC-I but not MHC-II
was observed on thymocytes of such mice and was accompanied with a pro-
gressive depletion of thymocytes as the disease progressed with 90% of double
positives being depleted by 9 days post infection. Staining studies with propidium
iodide and Annexin V revealed that the percent thymocytes undergoing apoptosis
had increased signiﬁcantly in animals infected with Japanese encephalitis virus.
Although similar changes in MHC-I expression were also observed in newborn
pups challenged with Japanese encephalitis virus, qualitative and quantitative
differences in thymocyte depletion were observed relative to the adult thymus.
These observations may have implications in the ability of the immune system to
respond to speciﬁc antigens and possible autoimmunity in survivors of Japanese
The thymus is a primary lymphoid organ that is responsible for maturation of T
cells and determines antigen speciﬁcity at the peripheral T cell level. Precursor
cells that migrate from the bone marrow into the thymus are CD4
negative (DN). Proliferation and differentiation of these cells generates immature
double positive (DP) cells that ﬁnally mature into Major Histocom-
patibility Complex (MHC) restricted self-tolerant single positive (SP) T cells.
This process of maturation involves the dual processes of positive and negative
selection [17, 10].