Geographical distribution of HIV-1 group O viruses in Africa.

OBJECTIVE: To determine to what extent HIV-1 group O strains are present in different African countries. MATERIALS AND METHODS: A total of 14,682 samples of sera from a range of patients from 12 different African countries were tested. All the sera were tested with an enzyme-linked immunosorbent assay (ELISA) using a combination of V3 peptides from ANT-70 and MVP-5180. Samples reactive in ELISA were retested in a line immunoassay (LIA-O). Samples reactive in ELISA were also retested with an in-house Western blot to determine the presence of antibodies to gp120 of HIV-1 ANT-70. Polymerase chain reaction was performed on HIV-1 group O and group O indeterminate sera. RESULTS: Of all the sera samples tested, only 19 sera had antibodies to group O V3 peptides exclusively and 46 were indeterminate for group O infection in LIA-O. The highest prevalence of HIV-1 group O infection among HIV-positive sera was observed in Cameroon (2.1%) and neighbouring countries, 1.1% in Nigeria and 0.9% in Gabon. The lowest rates were seen in west Africa: 0.07% in Senegal, 0.14% in Togo, 0.16% in Chad and 0.3% in Niger. Group O sera were observed in almost all the population categories tested. The ANT-70 V3 peptide in LIA-O was reactive with all of the sera considered to be HIV-1 group O antibody positive by LIA, versus 78.9% for the MVP-5180 peptide. Thirteen out of 19 group O samples of sera were tested in PCR. Eight samples were identified as group O by specific group O pol and/or V3 primers; in the remaining five samples no HIV RNA could be detected. Of the indeterminate sera samples, two were identified as group O. CONCLUSION: In eight of the 12 countries tested, antibodies to group O viruses were identified. Numbers of HIV-1 group O viruses are low. Their presence is not restricted to Cameroon and neighbouring countries but can also be found in west and south-east Africa.

PIP: An enzyme-linked immunosorbent assay (ELISA), using a combination of V3 peptides and ANT-70 and MVP-5180, was used to test 14,682 sera samples from people living in Burkina Faso, Burundi, Cameroon, Chad, Congo, Gabon, Mali, Niger, Nigeria, Senegal, Togo, and Zambia to examine the geographic spread of HIV-1 group O viruses in Africa. An in-house Western blot and a line immunoassay (LIA-O) were used to detect the presence of antibodies to gp120 of HIV-1 ANT-70 of samples reactive in ELISA and then a polymerase chain reaction (PCR) on HIV-1 group O and group O indeterminant sera. HIV-1 group O antibodies were present in 8 countries (Cameroon, Chad, Gabon, Niger, Nigeria, Senegal, Togo, and Zambia). Among these 8 countries, the prevalence of HIV-1 group O sera ranged from 2.1% in Cameroon to 0.07% in Senegal. Cameroon and its neighboring countries had a higher prevalence than the West African countries (0.9-2.1% vs. 0.07-0.3%) and Zambia. HIV-1 group O virus was more or less evenly distributed among the population groups tested. The ANT-70 V3 peptide in LIA-O had a higher reactivity rate with HIV-1 group O sera than MVP-5180 V3 peptide in LIA-O (100% vs. 78.9%). 8 of the 13 samples tested in PCR were identified as group O by specific group O pol and/or V3 primers. Among the remaining 5 indeterminant sera samples, 2 were identified as group O. Prospective studies are needed to monitor the true prevalence of HIV-1 group O viruses in Cameroon, its neighboring countries, and West Africa. They are also needed to determine the risk factors associated with group O infection. Monitoring these viruses will allow adaptation of HIV testing strategies for blood screening and serodiagnosis if required.

Virologic and serologic characteristics of a natural chimpanzee lentivirus infection.

This study set out to characterize the unique features of natural lentivirus infection in chimpanzees over time. The virologic and serologic characteristics of this infection were followed longitudinally in a naturally infected chimpanzee together with a small cohort of experimentally HIV-1-infected chimpanzees. The subsequent isolates from the naturally infected chimpanzee were all non-syncytium forming (NSI) versus syncytium forming in the experimentally infected animals. In contrast to HIV-1-infected chimpanzees virus load was higher and plasma viremia occurred but in a cyclic pattern. Serologic follow-up suggested the development of neutralizing antibodies with subsequent escape of new isolates. Interestingly, the sequence of the principal neutralizing (V3 loop) domain (of HIV-1) remained constant over time. Antibodies to peptides from the V3 loop were type specific. The occurrence of persistent, fluctuating plasma viremia and NSI-type virus variants of this natural lentivirus infection are unique characteristics not previously reported in experimentally infected chimpanzees.

Genomic cloning and complete sequence analysis of a highly divergent African human immunodeficiency virus isolate.

Analysis of the complete sequence of a human immunodeficiency virus (HIV) isolate (Ant70) obtained from a Cameroonian patient indicates that this virus is the most divergent strain within the HIV-1 family hitherto described. Comparison of the Pol protein, usually highly conserved within the HIV-1 family, shows only about 73% similarity with the HIVmm isolate, whereas for the more variable proteins such as envelope, similarities of 50% or lower are found. The principal neutralizing determinant (V3 loop) and the immunodominant region within gp41 also contain some unusual substitutions, which may have implications for protein function as well as for serological assays based on these regions. Phylogenetic analyses show that this isolate occupies a unique position relative to the human HIV-1 isolates and the recently described SIVcpz virus, indicating that this Cameroonian isolate may provide us with new insights into the origins of the HIV-1 family.

Isolation and partial characterization of an unusual human immunodeficiency retrovirus from two persons of west-central African origin.

An unusual human retrovirus was isolated from two patients with persistent generalized lymphadenopathy who originate from West-Central Africa and are currently residing in Belgium. Although the virus shared a number of the same biological and morphological properties as human immunodeficiency retrovirus type 1 (HIV-1) and HIV-2, significant antigenic differences could be demonstrated. Several of the viral proteins also differed in molecular weight from the corresponding HIV-1 and HIV-2 proteins. Partial chemical cleavage of the most highly conserved viral proteins resulted in patterns which differed from those of HIV-1 and HIV-2. Furthermore, nucleic acid hybridization experiments were capable of discriminating between the virus types. Sequence analysis of the viral U3 region revealed a unique enhancer organization not found in other immunodeficiency viruses. The data indicated that the new isolate is more closely related to HIV-1 than to HIV-2 but clearly differs in a number of important respects.

Sequence analysis of a highly divergent HIV-1-related lentivirus isolated from a wild captured chimpanzee.

Two strains of simian immunodeficiency viruses (SIV) isolated from chimpanzees (SIVCPZ-GAB and SIVCPZ-GAB2) originating from Gabon have previously been genetically characterized and shown to belong phylogenetically to the same lineage as the human immunodeficiency virus type 1 (HIV-1). We describe the sequence analysis of a third HIV-1-related virus, SIVCPZ-ANT, isolated from a wild captured chimpanzee originating from Zaire. This virus displayed the same genetic organization as HIV-1 and was found to fall on the same lineage as HIV-1 and SIVCPZ-GAB. Protein sequence identity with SIVCPZ-GAB ranged from 72% (Pol) to 48% (Env) for the structural proteins, while a particularly divergent Vpu was found (only 25% identity to SIVCPZ-GAB). The V3 regions of the SIVCPZ isolates were exceptionally conserved in contrast to the high divergence of V3 among HIV-1 isolates. However, SIVCPZ-ANT did not show a greater degree of sequence similarity with SIVCPZ-GAB than with HIV-1 isolates and represents a quite divergent outgroup of the HIV-1 lineage. Our data suggest multiple introductions of HIV-1 in the human population and shed new light on the origin of the HIV-1 pandemic.

Study of the dynamics of neutralization escape mutants in a chimpanzee naturally infected with the simian immunodeficiency virus SIVcpz-ant.

Here we report on the use of spectral map analysis of time-paired sequential neutralization data of 11 serum samples of a chimpanzee naturally infected with a simian immunodeficiency virus (SIVcpz-ant) and 8 primary consecutive SIVcpz-ant isolates, taken at about 4-month intervals. The analysis reveals the existence of three SIVcpz-ant isolate and serum neutralization clusters. Each cluster groups virus isolates and/or sera based on similarities of their neutralization spectra. On average, neutralization escape mutants emerged after 15 months and mounted a neutralization response approximately 8 months later. The entire gp160 regions of eight consecutive isolates were sequenced and analyzed by a new statistical method called polygram, which allowed the deduction of amino acid sequence motifs of gp160 which were specific for SIVcpz-ant isolates belonging to the same isolate neutralization clusters. Changes in specific amino acid quadruplets in V1, V2, C3, V4, V5, and CD4 domains of gp120 and gp40 were seen to correlate with the neutralization clusters with most of the specific changes occurring in the V4 region. This method of analysis may facilitate an understanding of the study of the dynamic interplay between human immunodeficiency virus (HIV) and host neutralization responses as well as providing possible insights into mechanisms of persistence of HIV-1-related lentiviruses in their natural hosts.