Did smallpox lead to HIV-1 resistance?

20 February 2009

10661_loresThe entry of HIV-1 into lymphocytes requires two cellular proteins, the receptor CD4, and a co-receptor, either CXCR4 or CCR5. Individuals who carry a mutation in the gene encoding CCR5, called delta 32, are resistant to HIV-1 infection. This observation was the basis for giving an AIDS patient a bone marrow transplant from a donor with the delta 32 mutation: his lymphocytes became resistant to HIV-1 infection, and he has been free of virus for over two years.

Approximately 10% of the human population carries the CCR5 delta 32 deletion (although it is rare in Africans and Asians). But HIV-1 is a recent invader of humans – it is believed to have crossed from chimpanzees around 1930. This length of time is far too short to have provided sufficient selection pressure to retain the CCR5 delta 32 mutation in humans. Instead, the selection pressure may have been provided by another human viral infection: smallpox.

Myxoma virus, a member of the poxvirus family, causes lethal disease in rabbits. Mouse cells that cannot be infected by this virus can be made susceptible to infection by expression of genes encoding several chemokine receptors, including CCR5. Furthermore, myxoma virus infection of CCR5-expressing mouse cells can be blocked with antibody to CCR5 or RANTES, its natural ligand. These observations indicate that CCR5 can serve as an entry receptor for myxoma virus.

Smallpox, a virus in the same family as myxoma virus, has been infecting humans for thousands of years – the earliest outbreaks are believed to have occurred before 1000 AD. The receptor for smallpox virus is not known, but if it is CCR5, then smallpox is the leading candidate for the selective pressure responsible for fixation of the CCR5 delta 32 HIV-1 resistance allele in modern Caucasians. 

A. S. Lalani (1999). Use of Chemokine Receptors by Poxviruses Science, 286 (5446), 1968-1971 DOI: 10.1126/science.286.5446.1968

  • http://http://www.qms-us.com QMS

    Oh that's a very complicated disease. How if you have an HIV? is there's a posibility to have small pox?

  • WondrousLeech

    I wonder if both viruses happen to have the molecular key to those proteins, and if that pattern on the virus happens to be part of what smallpox-killing immune cells respond to. If the smallpox VACCINE accidentally also defended against HIV-1, then the appearance of HIV-1 after smallpox vaccination ended might not be a coincidence.

  • http://www.virology.ws profvrr

    There isn't any more smallpox on the globe – it was eradicated years
    ago, the last case reported in 1979.

  • http://www.virology.ws profvrr

    The vaccine against smallpox is a different virus that does not cause
    smallpox. It would not have selected for people with the CCR5 delta 32
    mutation. Smallpox killed many people; the idea is that the survivors
    had the CCR5 mutation.

  • WondrousLeech

    I wonder if both viruses happen to have the molecular key to those proteins, and if that pattern on the virus happens to be part of what smallpox-killing immune cells respond to. If the smallpox VACCINE accidentally also defended against HIV-1, then the appearance of HIV-1 after smallpox vaccination ended might not be a coincidence.

  • http://www.virology.ws profvrr

    There isn't any more smallpox on the globe – it was eradicated years
    ago, the last case reported in 1979.

  • http://www.virology.ws profvrr

    The vaccine against smallpox is a different virus that does not cause
    smallpox. It would not have selected for people with the CCR5 delta 32
    mutation. Smallpox killed many people; the idea is that the survivors
    had the CCR5 mutation.