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Click Here "Measles and TB evolved from diseases of our cattle, influenza from a disease of pigs, and smallpox possibly from a disease of camels. The Americas had very few native domesticated animal species from which humans could acquire such diseases."

-Jared Diamond  

Stockpiling smallpox virus

For more than 30 years, the only remaining stocks of smallpox virus have been stored in the P4 freezers of Atlanta and Novosibirsk, Russia.  Arguments for maintaining the virus stocks include the need to assess antiviral agents for the treatment of smallpox, the need to test and develop safer vaccines for those at a higher risk of post-vaccination complications, and the need to develop enhanced diagnostic tests.  Further, there is a possibility that additional stocks of the virus are being kept in unknown locations.  To the contrary, the primary benefit in destroying the known stocks is a reduction in the probability that smallpox cases will reappear.  Additionally, destroying the stocks of smallpox would make good on the commitment that the US made in 1990 to destroy stocks after the genome had been sequenced and it would circumvent pressures to return stocks to their country of origin. 

Mack, Thomas. "Stockpiling Smallpox Virus". BMJ 2007; 334: 760.

Containing a large bioterrorist smallpox attack

A stochastic simulation model of the spread of smallpox in the aftermath of a large bioterrorist attack suggested that surveillance & containment - isolation of known cases and vaccination of their close contacts - would be sufficient to contain a large, international release of variola virus.  The results indicate that preemptive vaccination of hospital workers and reactive vaccination of the target population would help limit the spread of the virus, but would represent a resource-intensive endeavor.  Most importantly, prevaccination of the general population was deemed unnecessary as a preventive measure, should an attack occur.

Ira Longini, Elizabeth Halloran, Azhar Nizam, et al. "Containing a large bioterrorist smallpox attack: a computer simulation approach". International Journal of Infectious Diseases 2007; 11(2): 98-108.

Cowpox Virus Evades CTL Recognition and Inhibits Intracellular Transport of MHC Class I Molecules

In the wake of smallpox eradication, the main orthopoxviruses infecting humans are zoonotic infections by monkeypox virus (MPV) and cowpox virus (CPV).  It has been determined that CPV evades recognition by T cells from VV-immunized individuals; this evasion is not due to a lack in cross-reactive T cells, but rather is an active immune evasion process.  Further, CPV (but not VV) inhibits the intracellular transport of MHC I molecules.  These new findings are critical, for understanding the pathogenesis of virulent orthopoxvirus infection will be key in developing both more advanced vaccines and antiviral therapies.

Anindya Dasgupta, Erika Hammarlund, Mark Slifka, et al. "Cowpox Virus Evades CTL Recognition and Inhibits the Intracellular Transport of MHC Class I Molecules". The Journal of Immunology 2007; 178: 1654-1661.

Effect of Oral Treatment with S-HPMPA on Cowpox or Vaccinia Virus Infections in Mice

A 2007 study indicated that, contrary to prior belief, oral HDP-(S)-HPMPA and ODE-(S)-HPMPA were both highly effective (P < 0.001) at preventing cowpox- and vacccinia-induced mortality when administered 48 or even 72 hours postinfection.   Protection against both viruses was associated with a significan reduction of virus replication in the liver, spleen, and kidney.  This data indicates that both compounds are active when given orally against lethal CPV and VV infections in mice - a fact that warrants further investigation on the potential of these orally active compounds in treatment of human orthopoxvirus infection.

Debra Quenelle, Deborah Collins, Bridgett Herrod, et al. "Effects of Oral Treatment with Octadecyloxyethyl-(S)-HPMPA on Cowpox or Vaccinia Virus Infections in Mice". Antimicrobial Agents and Chemotherapy 2001; 51(11): 3940-3947.

Risk factors for Human Monkeypox in the United States

In the aftermath of the 2003 monkeypox (MPXV) outbreak in the U.S., researchers initiated a case-control study with the objective of evaluating risk factors for animal-to-human MPXV transmission.  They found that cases were significantly more likely than controls to have had daily exposure to a sick animal, cleaned cages and bedding of a sick animal, or touched a sick animal.  The fact that daily exposure to infected prairie dogs was associated principally with disease (rather than simply infection) indicates that increasing the intensity or duration of exposure to viral inoculum may increase the probability for overt illness.

Reynolds. "Spectrum of Infection and Risk Factors for Human Monkeypox, United States, 2003". Emerging Infectious Diseases 2007; 13: 1332.

Tropism of Tanapox virus infection in primary human cells

Tanapox virus (TPV) causes a benign zoonotic disease in humans - symptoms resemble a mild version of human monkeypox.  To better understand the mechanisms of TPV pathogenesis, researchers examined the tropism and replication characteristics of TPV in several primary human cells.  Results indicated that CD14+ cells, or monocytes, were the primary target for TPV infection; however, once monocytes differentiated into macrophages, they ceased to support replication of TPV.  This tropism provides key insights into the basis for the self-limiting pathogenicity of TPV in humans.

Steven Nazarian, John Barrett, Marianne Stanford, et al. "Tropism of Tanapox virus infection in primary human cells" Virology 2007; 368(1).