Large animal model Equine infectious anemia virus (EIAV) Visna-maedi virus (VMV) Caprine arthritis-encephalitis virus (CAEV)

-Cause by lentivirus (not closely related to HIV). -Not much practically use in research as the smaller animal. -Use for study about pathogenesis of retrovirus infection -The viruses are not T-lymphotropic and do not cause immunodeficiency.

Clinical manifestation of lentivirus infection in natural hosts

3.Conclusion - Advantages and disadvantages between different species. - Benefits and problems of using animal model - Extrapolation - Future prospects

Chimpanzee -98.5% genetic resemble to human. -Can infected with HIV-1. -Good model for study cross reactive immune response. -It rarely develop disease. -It cant be use in sufficient numbers to provide statistically significant results. -Large size. -Expensive. -Not easy to handle.

Monkeys -About 93% genetic similarity to human. -Can provide enough numbers for study. -Can be infected by many type of SIV,HIV2 -Results from different SIV strain can not be reliably extrapolate to one another. -Not easy to handle. -Large size. -expensive -Hight risks of zoonosis.

Mice -Small size,easy to handle inexpensive. -High reproductive,short generation time and life span. -Know about genetic makeup. -Large number available in many strain. -Can create desired system by genetic engineering. -SCID mice does not have a standard human immune system. -Incomplete and low number of repopulating human lymphoid cells -SCID mice does not develop AIDS like disease

Cats -Not large size. -Not difficult to handle. -Not much expensive. -Can be infected with FIV,FeLV and develop immunodeficiency like syndrome. -Cause nearly identical disease to HIV infection. -Cat is far related genetic to human. -FIV,FeLV are not closely related to HIV.

Benefits and problems of using animal model Benefits -Animal studies of toxicity, efficacy and pharmacokinetics provide valuable scientific information toward identifying potentially useful antiviral agents -Helps approximate how drugs/vaccines might perform in human. -Helps to understand some certain mechanism of disease and therapeutic agent observed in animal model. -Study in animal is able to induced certain condition that can not be done in human.

Problems -Preclinical studies generally are inadequate to predic whether an anti viral agent will be both effective and safe when administered to human.(it is not until the agent enters clinical trail in humans that is potential can be ascertained). -There are large differences in the host cell enzymes affinities for a specific antiviral compound among species. -Difficulties between interspecies evaluation.

Extrapolation Because there’re different between species and every animal behave not same to human, to minimize misinterprete of the results,the extrapolation should meet some general requirement. -Taking a plurispecies approach. -Metabolic patterns and speed must match between species. -Confounding variables of metabolism must be controll. -Experimental design and the life situation of the target species must correspond.

Future prospects Most model have their great potential in pathogenesis,immune- response analysis, vaccines and therapies study. Accordingly the challenge for the future is to utilize the increasing knowledge of molecular mechanism of HIV and HIV replication to elucidate all aspects of the virus host relationships fully and thereby to understand mechanism of pathogenesis in AIDS further. Question like antibody enhancement of virus infection, induction of auto immunity, presence of viral super antigens responsible for T cell depletion and development of immune cell dysfunction and tumours can should all be investigated in animal model in the near future and there’re tendency to developments in the field of small animal models for HIV disease.