CCR5∆32 and SDF1 3'A: Gene Variants, Expression and Influence on Biological Markers for the Clinical Progression to AIDS among HIV-1 Virus Controllers in a Mixed Population of the Amazon Region of Brazil.

CCR5Δ32 and SDF1-3'A polymorphisms were investigated in a cohort of viremia controllers, without the use of therapy, along with their influence on CD4+ T lymphocytes (TLs), CD8+ TLs, and plasma viral load (VL). The samples were analyzed from 32 HIV-1-infected individuals classified as viremia controllers 1 and 2 and viremia non-controllers, from both sexes, mostly heterosexuals, paired with 300 individuals from a control group. CCR5∆32 polymorphism was identified by PCR amplification of a fragment of 189 bp for the wild-type allele and 157 bp for the allele with the ∆32 deletion. SDF1-3'A polymorphism was identified by PCR, followed by enzymatic digestion (restriction fragment length polymorphism) with the Msp I enzyme. The relative quantification of gene expression was performed by real-time PCR. The distribution of allele and genotype frequencies did not show significant differences between the groups. The gene expression of CCR5 and SDF1 was not different between the profiles of AIDS progression. There was no significant correlation between the progression markers (CD4+ TL/CD8+ TL and VL) and the CCR5∆32 polymorphism carrier status. The 3'A allele variant was associated with a marked loss of CD4+ TLs and a higher plasma VL. Neither CCR5∆32 nor SDF1-3'A was associated with viremia control or the controlling phenotype.

HTLV in South America: Origins of a silent ancient human infection.

The description of the first human retrovirus, human T-lymphotropic virus 1 (HTLV-1), was soon associated with an aggressive lymphoma and a chronic inflammatory neurodegenerative disease. Later, other associated clinical manifestations were described, affecting diverse target organs in the human body and showing the enormous burden carried by the virus and the associated diseases. The epidemiology of HTLV-1 and HTLV-2 showed that they were largely distributed around the world, although it is possible to locate geographical areas with pockets of low and very high prevalence and incidence. Aboriginal Australians and indigenous peoples of Brazil are examples of the large spread of HTLV-1 and HTLV-2, respectively. The epidemiological link of both situations is their occurrence among isolated, epidemiologically closed or semi-closed communities. The origin of the viruses in South America shows two different branches with distinct timing of entry. HTLV-1 made its probable entrance in a more recent route through the east coast of Brazil at the beginning of the slave trade from the African continent, starting in the 16th century and lasting for more than 350 years. HTLV-2 followed the ancient route of human migration from the Asian continent, crossing the Behring Strait and then splitting in South America as the population became separated by the Andes Mountains. By that time, HTLV-2c probably arose and became isolated among the indigenous populations in the Brazilian Amazon. The study of epidemiologically closed communities of indigenous populations in Brazil allowed tracing the most likely route of entry, the generation of a new molecular subtype (HTLV-2c), the elucidation of the vertical transmission of HTLV-2, the intrafamilial aggregation of cases and the escape and spread of the virus to other areas in Brazil and abroad. Despite the burden and impact of both viruses, they are maintained as silent infections among human populations because 1, health authorities in most South American countries in which national surveillance is poor have little interest in the disease, 2, the information is commonly lost as indigenous groups do not have specific policies for HTLV and other sexually transmitted infections, and 3, health access is not feasible or properly delivered.