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Smallpox is a contagious disease caused by the Variola major virus, a double-stranded DNA virus from the poxvirus family.

Transmission mainly occurs through inhalation of virus-laden droplets or contact with infectious dried scabs.

Upon inhalation, the virus targets the mucosal surfaces of the respiratory tract, attaching to the cell surface molecules on respiratory epithelial cells.

This binding triggers viral entry into the cell by endocytosis, initiating replication inside the cytoplasm.

Newly formed viral particles are released and engulfed by macrophages, which transport them to nearby lymph nodes.

Here, the virus is released, which multiplies further before entering the bloodstream and spreading throughout the body.

After an incubation period of about 7 days, patients develop a high fever and skin rashes.

The rash begins as flat red macules that progress to raised papules. These then fill with fluid, forming vesicles, and later with pus, forming pustules.

Eventually, the pustules crust over, forming scabs that leave deep scars.