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INFECTIOUS DISEASE

BACTERIOLOGY IMMUNOLOGY MYCOLOGY PARASITOLOGY VIROLOGY

VIDEO LECTURE

VIROLOGY - CHAPTER   SEVEN    

PART ELEVEN

HUMAN IMMUNODEFICIENCY VIRUS AND AIDS  

POPULATION POLYMORPHISM

Dr Richard Hunt

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POPULATION POLYMORPHISM AND HIV VARIANTS

Population polymorphism results from the high error rates of reverse transcriptase and RNA polymerase II which are used to replicate the viral genome. The error rate is 1 in 2000 - 10,000 nucleotides. This, together with the high rate of CD4+ cell production and infection, means that every possible single point mutation in the viral genome arises daily and almost 1% of all possible double mutations occur each day. As a result, the virus isolated from an AIDS patient is very different from the original infecting virus. Distinct sub-strains differ in cell tropism. Some form syncytia, some do not. As has been already noted, the non-syncytium-inducing macrophage-tropic type is probably the infectious form (Note: most vaccines have been made against the syncytium-inducing form of HIV-1 and polymorphism poses a great obstacle to the successful development of a vaccine). The major variable protein is Gp120 and, within a single patient, HIV-1 commonly varies by 1 - 6% in the ENV gene. There are some conserved sites in Gp120 in which mutations are presumably  non-viable (e.g. the CD4 binding site). But very often glycosylation masks these conserved sites (which also poses a problem for vaccine development). Gp41 is not as glycosylated and the fusion site needs to be conserved (this may be a possible vaccine site).

Compared to variation within an individual, there is a lot greater variability around the world. HIV-1 genetic subtypes differ by up to 30% in the amino acid sequence of the ENV gene. There are at least 10 subtypes of HIV-1.

Not only is the reverse transcriptase mutation rate a problem. It is possible for a person to be infected by different HIV-1 subtypes resulting in cells becoming co-infected. Resultant viruses have one RNA from one subtype and one from the other. On later rounds of infection recombination occurs. It has been found that a recombinant subtype (HIV-1E) is spreading globally. The impact of these evolving subtypes is great since they may affect the efficacy of tests for infected blood. Moreover, they have to be taken into account when thinking of a vaccine. There is also the possibility that there may be significant differences in the transmissibility of different subtypes (HIV-1 is much more transmissible than HIV-2).
 

 
 

STRATEGIES TO COMBAT VIRUS

Chemotherapy

Most anti-HIV drugs are toxic. In addition, present anti-HIV chemotherapy does not stop infection and is unlikely to cure the infected host (see chemotherapy chapter). The most we can hope for is suppression of virion production making AIDS a more tractable disease. Recently great strides towards this goal have made (see appendix 3).

Education

HIV is (fortunately) not highly infectious. It can be avoided by taking the correct precautions. This approach has been very successful in certain countries in containing the spread of AIDS.

Vaccine

This is the best way to protect against  infection. But HIV is a retrovirus and this poses enormous problems for vaccine development (see appendix 1).

 

 

   

 


OTHER HIV SECTIONS

PART I HUMAN IMMUNODEFICIENCY VIRUS AND AIDS

PART II HIV AND AIDS, THE DISEASE

PART III COURSE OF THE DISEASE

PART IV PROGRESSION AND COFACTORS

PART V STATISTICS

PART VI  SUBTYPES AND CO-RECEPTORS

PART VII  COMPONENTS AND LIFE CYCLE OF HIV

PART VIII  LATENCY OF HIV

PART IX GENOME OF HIV

PART X  LOSS OF CD4 CELLS

PART XI   POPULATION POLYMORPHISM

APPENDIX I  ANTI-HIV VACCINES

APPENDIX II  DOES HIV CAUSE AIDS?

APPENDIX III  ANTI-HIV CHEMOTHERAPY

 

 

 

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