**3.2 Rubella**

Despite the availability of an effective vaccine, over 100,000 cases of congenital rubella syndrome are reported every year. Congenital rubella infection occurs via transplacental transmission of the RNA virus to the fetus during maternal viremia [104]. The infection may be asymptomatic, present with mild common cold-like symptoms, or devastating. Clinical features such as fetal-neonatal cataract and glaucoma, microphthalmia; patent ductus arteriosus, cardiac septal defects, pulmonary vascular stenosis, sensorineural deafness, fetal growth restriction, thrombocytopenia, anemia, hepatosplenomegaly, hepatitis, direct hyperbilirubinemia, chronic diffuse interstitial pneumonia, osseous changes, and even chromosomal abnormalities are grouped in congenital rubella syndrome. Fetal infection is found to cause necrosis, apoptosis, and division errors of cells involved in organogenesis, resulting in malformations. The mitotic activity is noted to be reduced in rubellainfected cells. Another potential mechanism is that of a direct viral invasion into vasculatures causing tissue necrosis without inflammation (**Figure 5**) [105]. The capsid of the rubella virion (RV) plays an important role in mitochondrial damage and viral replication complexes, as evidenced by immunogold electron microscopy and indirect immunofluorescence studies. Cardiolipin is a phospholipid associated exclusively with mitochondria, and its presence in rubella virions suggests the involvement of the internal mitochondrial membrane of cells in viral proliferation. Both the mitochondrial distribution and morphology are abnormal in RV-infected cells, and the mitochondria tend to cluster in the perinuclear region along with viral replication complexes. In advanced infection electron-dense plaques between opposing mitochondria are formed, and the mitochondrial cristae may be lost in RV-infected cells [106]. The risk of congenital malformation is low after 17 weeks of IU life. It is thought that the immune response mechanisms (immunoglobulins like IgM, IgG, and IgA, T cells, natural killer cells, and interferons) appear during the second half of pregnancy and are not sufficiently mounted against the infection during the first trimester [107].
