HIV-1 recombinants with multiple parental strains in low-prevalence, remote regions of Cameroon: Evolutionary relics?

<p>Abstract</p> <p>Background</p> <p>The HIV pandemic disseminated globally from Central West Africa, beginning in the second half of the twentieth century. To elucidate the virologic origins of the pandemic, a cross-sectional study was conducted of the genetic diversity of HIV-1 strains in villagers in 14 remote locations in Cameroon and in hospitalized and STI patients. DNA extracted from PBMC was PCR amplified from HIV(+) subjects. Partial <it>pol </it>amplicons (N = 164) and nearly full virus genomes (N = 78) were sequenced. Among the 3956 rural villagers studied, the prevalence of HIV infection was 4.9%; among the hospitalized and clinic patients, it was 8.6%.</p> <p>Results</p> <p>Virus genotypes fell into two distinctive groups. A majority of the genotyped strains (109/164) were the circulating recombinant form (CRF) known to be endemic in West Africa and Central West Africa, CRF02_AG. The second most common genetic form (9/164) was the recently described CRF22_01A1, and the rest were a collection of 4 different subtypes (A2, D, F2, G) and 6 different CRFs (-01, -11, -13, -18, -25, -37). Remarkably, 10.4% of HIV-1 genomes detected (17/164) were heretofore undescribed unique recombinant forms (URF) present in only a single person. Nearly full genome sequencing was completed for 78 of the viruses of interest. HIV genetic diversity was commonplace in rural villages: 12 villages each had at least one newly detected URF, and 9 villages had two or more.</p> <p>Conclusions</p> <p>These results show that while CRF02_AG dominated the HIV strains in the rural villages, the remainder of the viruses had tremendous genetic diversity. Between the trans-species transmission of SIV_cpzand the dispersal of pandemic HIV-1, there was a time when we hypothesize that nascent HIV-1 was spreading, but only to a limited extent, recombining with other local HIV-1, creating a large variety of recombinants. When one of those recombinants began to spread widely (i.e. became epidemic), it was recognized as a subtype. We hypothesize that the viruses in these remote Cameroon villages may represent that pre-epidemic stage of viral evolution.</p

Lipid peroxidation and total cholesterol in HAART-naïve patients infected with circulating recombinant forms of human immunodeficiency virus type-1 in Cameroon.

BackgroundHIV infection has commonly been found to affect lipid profile and antioxidant defense.ObjectivesTo determine the effects of Human Immunodeficiency Virus (HIV) infection and viral subtype on patient's cholesterol and oxidative stress markers, and determine whether in the absence of Highly Active Antiretroviral Therapy (HAART), these biochemical parameters could be useful in patient's management and monitoring disease progression in Cameroon. For this purpose, we measured total cholesterol (TC), LDL cholesterol (LDLC), HDL cholesterol (HDLC), total antioxidant ability (TAA), lipid peroxidation indices (LPI), and malondialdehyde (MDA) in HIV negative persons and HIV positive HAART-naïve patients infected with HIV-1 group M subtypes.MethodsWe measured serum TC, LDLC, HDLC, plasma MDA, and TAA concentrations, and calculated LPI indices in 151 HIV-positive HAART-naïve patients and 134 seronegative controls. We also performed gene sequence analysis on samples from 30 patients to determine the effect of viral genotypes on these biochemical parameters. We also determined the correlation between CD4 cell count and the above biochemical parameters.ResultsWe obtained the following controls/patients values for TC (1.96±0.54/1. 12±0. 48 g/l), LDLC (0. 67±0. 46/0. 43±0. 36 g/l), HDLC (105. 51±28. 10/46. 54±23. 36 mg/dl) TAA (0. 63±0. 17/0. 16±0. 16 mM), MDA (0. 20±0. 07/0. 41±0. 10 µM) and LPI (0. 34±0. 14/26. 02±74. 40). In each case, the difference between the controls and patients was statistically significant (pConclusionThese results show that HIV infection in Cameroon is associated with significant decrease in TAA, LDLC, HDLC and TC, and increased MDA concentration and LPI indices which seem to be linked to the severity of HIV infection as assessed by CD4 cell count. The data suggests increased oxidative stress and lipid peroxidation in HIV-infected patients in Cameroon, and an influence of CRFs on TC and MDA levels

Molecular epidemiology of GB type C virus among individuals exposed to hepatitis C virus in Cameroon

GB Virus Type C (GBV-C), a blood-borne flavivirus currently infects about one sixth of the world’s population. Its transmission has been reported through parenteral, sexual and vertical routes. Unusually for RNA viruses, it exhibits a high degree of conservation of the polyprotein sequence. The geographical distribution of GBV-C suggests an African origin and a long-term co-evolution in the human population but without any known pathogenicity. The aim of this study was to describe the different sub-types of this virus in Southern Cameroon. We studied the genetic epidemiology of GBV-C among rural populations where many HIV-1 and HCV genotypes have been identified. Plasma samples of 345 subjects with evidence of HCV exposure were tested for GBV-C infection. To detect GBV-C RNA, reverse transcription followed by a nested PCR of 5’UTR were performed. Direct sequencing and phylogenetic studies using PHYLIP, PAUP* and SimPlot were carried out. In total, 31 GBV-C RNA-positive samples were detected giving a prevalence of 9.0% among HCV-exposed individuals. Phylogenetic analysis of the 5’UTR showed two distinct clusters: Genotype 1 and Genotype 2. Twenty-eight isolates (8.0%) clustered with Genotype 1 and 3 (1.0%) with Genotype 2. More than one genotype of GBV-C is prevalent in Cameroon of which GBV-C Genotype 1 is more common, confirming reports in the literature. Studying the near full-length genome sequences of GBV-C isolates from primates in this region may provide clues of viral recombination, evolution and origin

Distribution of HIV-1 subtypes in patients by sex and CD₄ cell counts.

<p>Distribution of HIV-1 subtypes in patients by sex and CD₄ cell counts.</p

Demographics and clinical characteristics of participants.

<p>Demographics and clinical characteristics of participants.</p

Comparison of different biochemical parameters between patients and controls.

<p>Every value is the mean ± standard deviation. SD = Standard deviation.</p

Phylogenetic tree of the different subtypes of HIV-1 group M included in the study (<i>460 bp encoding amino acid 132 of p24 to amino acid 40 of p7 from the gag gene)</i>.

<p>Cons = reference sequences; G = sample.</p

Biochemical parameters in HIV-infected patients, correlated with CD4 using Pearson correlation coefficient.

*<p>Significant Pearson correlation (P<0, 05 at a bilateral level).</p>**<p>Significant Pearson correlation (p<0, 01 at a bilateral level).</p