The high prevalence of PRI-associated substitutions represent natural polymorphisms occurring in PRI-naive patients infected with HIV-1 strains of subtypes A-H. The significance of distinct mutation patterns identified for subtype B and non-B strains warrants further clinical evaluation. A global HIV-1 protease database is fundamental for the investigation of novel PRI.
Human herpesvirus-8 (HHV-8) variants have been found heterogeneously distributed among human populations living in diverse geographic regions, but their differential pathogenicity in Kaposi's sarcoma development remains controversial. In the present study, HHV-8 variant distribution has been analyzed in classic, iatrogenic, endemic as well as epidemic Kaposi's sarcoma (KS) during pre-AIDS and AIDS period (1971-2008) in countries with different KS incidence rate. DNA samples from cutaneous KS lesions of 68 patients living in Africa (n=23, Cameroon, Kenya and Uganda), Europe (n=34, Greece and Italy) and North America (n=11) have been subjected to PCR amplification of HHV-8 ORF 26, T0.7, K1 and K14.1/15, followed by direct nucleotide sequencing and phylogenetic analysis. Among the 23 African samples, the majority of HHV-8 ORF 26 variants clustered with the subtype R (n=12) and B (n=5). Conversely, the viral sequences obtained from 45 European and North European tumors belonged mainly to subtype A/C (n=36). In general, HHV-8 and K1 variant clustering paralleled that of ORF 26 and T0.7. Genotyping of the K14.1/15 loci revealed a large predominance of P subtype in all tumors. In conclusion, comparison of the HHV-8 sequences from classic or endemic versus AIDS-associated KS showed a strong linkage of the HHV-8 variants with specific populations, which has not changed during AIDS epidemic.
This study suggests that although subtype A may have a slower progression than D, HIV-1 envelope subtype is not a major factor in determining the progression of HIV-1 disease in a rural population in Uganda.
Introduction
Human herpesvirus 8 (HHV8), the infectious cause of Kaposi sarcoma (KS), varies dramatically across Africa, suggesting co-factors correlated with large-area geographical or environmental characteristics may influence risk for infection. Variation of HHV8 seropositivity across small-area regions within countries in Africa is unknown. We investigated this issue in Uganda, where KS distribution is uneven and well-described.
Methods
Archival samples from individuals aged 15–59 years randomly selected from a nationally-representative 2004/05 HIV/AIDS serobehavioral survey were tested for HHV8 seropositivity using enzyme immunoassays based on synthetic peptides from the K8.1 and orf65 viral genes. Adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) of association of HHV8 seropositivity with demographical risk factors were estimated.
Results
Among 2681 individuals tested, HHV8 seropositivity was 55.4%. HHV8 seropositivity was lower in females than males (aOR 0.82, 95% CI 0.69–0.97), and increased 2.2% (95% 1.0%-3.6%) per year of age in females and 1.2% (95% CI 1.0–2.3%) in males, inversely associated with education (ptrend=0.010), and was elevated in West Nile compared to Central region (aOR 1.49, 95% CI 1.02–2.18) but not in other regions.
Conclusions
Our findings suggest that HHV8 seropositivity in Uganda may be influenced by co-factors correlated with small-area geography, age, gender, and education.
Mucosal, cutaneous and Epidermodysplasia verruciformis (EV)-related human papillomaviruses (HPVs) were searched by broadspectrum PCR in 86 conjunctival neoplasia biopsies and 63 conjunctival non-neoplastic control tissue from Ugandan subjects. Seven different EV-related HPV types, including a putative new HPV, and two mucosal HPVs were detected in 25% (14 out of 56) of HIVpositive, in 10% (three out of 30) of HIV-negative conjunctival neoplasia samples, and rarely (0 -1.6%) in control subjects. The absence of high-risk HPVs and the low detection frequency of EV-related HPV types in more advanced tumour stages (10%) raise doubts about their role in conjunctival carcinomas.
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