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Pathogen Page

Variola virus

I. General Information

1. NCBI Taxonomy ID:

2. Disease:

Smallpox

3. Introduction

The poxviruses are a family of large, enveloped deoxyribonucleic acid (DNA) viruses. The most notorious poxvirus is variola, the causative agent of smallpox. Smallpox was an important cause of morbidity and mortality in the developing world until recent times. Since the host range of the variola virus is confined to humans, aggressive case identification and contact vaccination were ultimately successful in controlling the disease. The last occurrence of endemic smallpox was in Somalia in 1977, and the last human cases were laboratory-acquired infections in 1978. By 1980, the World Health Organization (WHO) General Assembly ratified the declaration of success made by the Global Commission for the Certification of Smallpox Eradication (PathPort).

4. Microbial Pathogenesis

Smallpox is a viral disease unique to humans. To sustain itself, the virus must pass from person to person in a continuing chain of infection and is spread by inhalation of air droplets or aerosols. There are three principal routes of viral infection corresponding to the three principal surfaces of the body: the respiratory tract, the alimentary tract, and the skin. Minor routes of infection include the urinary and genital tracts and the conjunctiva. Although congenital infection occasionally occurred in smallpox, it was of no epidemiologic importance. The infectious dose is unknown but is believed to be only a few virions (Henderson, 1999).
It is assumed to be low, 10 to 100 organisms (Franz et al., 1997).
Variola is most effectively spread via the respiratory route with as little as ten plaque-forming units contained within aerosolized saliva able to transmit the infection from person to person (Hassett, 2003).
Variola virus is highly stable and retains its infectivity for long periods outside the host. It is infectious by aerosol, but natural airborne spread to other than close contacts is controversial. Approximately 30% of susceptible contacts became infected during the era of endemic smallpox, and the WHO eradication campaign was predicated on close person-to-person proximity being required for transmission to occur reliably. Nevertheless, variola virus's potential in low relative humidity for airborne dissemination was alarming in two hospital outbreaks. On natural exposure to aerosolized virus, variola travels from the upper or the lower respiratory tract to regional lymph nodes, where it replicates and gives rise to viremia, which is followed soon thereafter by a rash (PathPort).

5. Host Ranges and Animal Models

Variola virus is considered to be a host-restricted poxvirus, with humans as the reservoir host and no zoonotic hosts known. However, the virus does replicate well in most mammalian cell cultures (McFadden, 2005).

6. Host Protective Immunity

Both cellular and humoral immune response are important in protection against smallpox. In mouse models of vaccinia infection, extensive studies have shown that passive immunotherapy with immune serum or monoclonal antibodies are protective. Antiviral antibody could protect mice efficiently even if CD4+ or CD8+ T cells were depleted prior to challenge. However, in B-cell-deficient or MHC II-deficient mice, which are unable to elicit effective antibody responses, strong antiviral T-cell responses played an important role in protecting against disease following viral challenge. Studies using non-human primates infected with lethal monkeypox showed that the smallpox vaccine-induced antibody responses were both necessary and sufficient for protection against lethal monkeypox infection. In humans, cellular immunity played the most important role in protective immunity in humans against primary poxvirus infections based on the severe complications following smallpox vaccination of children with genetic T-cell deficiencies. Following vaccination, strong antiviral antibody responses are likely to be the main effector mechanism responsible for protection against secondary infection (Amanna et al., 2006).

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