Francis Barin

SEROLOGICAL EVIDENCE FOR VIRUS RELATED TO SIMIAN T-LYMPHOTROPIC RETROVIRUS III IN RESIDENTS OF WEST AFRICA

Serological evidence is presented here suggesting that a virus closely related to simian T-lymphotropic virus type III (STLV-III) infects man in Senegal, west Africa, a region where AIDS or AIDS-related diseases have not yet been observed. 25 sera from Senegalese individuals that were positive for antibodies to HTLV-III by enzyme-linked immunosorbent assay were examined for antibodies to HTLV-III and STLV-III by western blotting. Sera from individuals originating from regions where AIDS has been reported, such as the United States and Burundi (central Africa), reacted best with antigens of HTLV-III, although antibodies that cross-reacted with STLV-III p24 were also detected. Conversely, sera originating from Senegalese people reacted better with STLV-III than with HTLV-III. This was exemplified by the absence of reactivity in sera from both monkeys and Senegalese people to p41, an antigen regularly detected by sera from antibody positive individuals originating from central Africa or from the United States. In contrast sera from central Africa or the United States did not react with p32, the putative envelope transmembrane protein of STLV-III that is regularly detected by sera from both monkeys and antibody-positive Senegalese people. These results suggest that certain healthy Senegalese people have been exposed to a virus that is more closely related to STLV-III than to HTLV-III. The existence and study of such virus variants potentially with differential pathogenicity may provide important information for the development of an AIDS virus vaccine.

A STLV-III related human retrovirus, HTLV-IV: analysis of cross-reactivity with the human immunodeficiency virus (HIV).

A category of viruses has been identified which is related to human immunodeficiency virus (HIV) but is more closely related to a group of simian retroviruses (STLV-III). These viruses named HTLV-IV, LAV-II, or SBL-6669, are prevalent in West-Africa. In this study, we analysed the cross-reactivity at the protein level between HTLV-IV and HIV (HTLV-IIIB). The results indicate that most people infected with HTLV-IV have antibodies that react to the major gag protein of HIV p 24. There is also a high degree of immunologic cross-reactivity between the pol gene products of HIV and HTLV-IV. Among these the endonuclease/integrase is more conserved than the reverse transcriptase. In contrast, the envelope glycoproteins that are the most frequently detected antigens by antibodies from exposed individuals are serotype specific. These data make the env gene products the most interesting antigens for serotype specific diagnosis of human retroviruses infections.

The Biology of HIV-1 and HIV-2 in Africa

As a result of rapidly expanding knowledge of the family of human retroviruses 2 new virus types related to human immunodeficiency virus (HIV) have been identified: HIV-2 and the closely related simian immunodeficiency virus (SIV)-2. These 2 viruses are similar to HIV-1 in that they demonstrate tropism to the T4 lymphocyte but differ from HIV-1 in terms of their unique open reading frame termed X. The major viral antigens of HIV-2 bear striking similarity and cross-reactive epitopes with the viral antigens of HIV-1. The close antigenic relationship of HIV-1 and HIV-2 has created new problems for serologic diagnosis and currently utilized HIV-1 immunoassays have shown variable ability in detecting HIV-2 antibody-positive samples. At present immunoblot and/or radioimmunoprecipitation analysis with both HIV-1 and HIV-2 virus types and the presence of antibodies to env products is necessary to distinguish these infections. Although the clinical picture of endstage acquired immunodeficiency syndrome (AIDS) appears to be similar in patients infected with HIV-1 and HIV-2 epidemiological and clinical studies suggest that the 2 viruses differ in pathogenicity. In West Africa a prevalence of HIV-2 infection of 0.2-9.2% has been detected in healthy adult populations while rates of HIV-1 are much lower. Sexually active risk groups such as female prostitutes and those with sexually transmitted diseases in these countries also demonstrate a significantly higher seroprevalence for HIV-2. In Burkina Faso and the Ivory Coast however significant rates of infection with both viruses are seen in high-risk populations. Serological surveys conducted in African countries outside of West Africa have failed to demonstrate evidence of HIV-2 infection despite variable levels of HIV-1 infection. On the other hand increased international travel can be expected to enhance the spread of HIV-2 infection outside of West Africa. A better understanding of the natural history and clinical significance of HIV-2 infection is essential for AIDS prevention and control programs worldwide.

Relationship of simian T-lymphotropic virus type III to human retroviruses in Africa.

HTLV-I has common characteristics of a simian retrovirus (STLV-I) such as extremely cross reactive major viral antigens. Further the major proteins of HTLV-III/HIV are similar to and cross react with those of STLV-III which causes an immunodeficiency syndrome similar to AIDS in macaque monkeys. It appears however that even though STLV-III has been found in green monkeys it does not adversely affect them. These similarities suggest that these viruses have a common ancestry. In their quest for more information on commonality between simian lymphotropic viruses and human retroviruses researchers found that antibodies of healthy prostitutes in West Africa reacted with related antigens of STLV-III e.g. the p24 p55 and gp 120/160 antigens. Researchers then isolated this human retrovirus and called it HTLV-IV. The prostitutes were healthy at the time of examination and 15 months later continued to show no symptoms of AIDS. This differs from global seroepidemiologic data of individuals with HTLV-III/HIV who upon exposure eventually develops AIDS related complex or AIDS. Present evidence shows that a number of related T-lymphotropic viruses affect their respective hosts pathogenically different. Further research may lead to the identification of distinctive structural and mechanistic differences responsible for the pathogenicity of the AIDS virus (HTLV- III/HIV). Research has shown that env-related antigens of HTLV-III/HIV STLV-III and HTLV-IV all cross react which means that common conserved regions of these viruses are immunogenic. Additional research marking these cross-reactive epitopes can provide the basis for the development of an AIDS vaccine.