The homeobox gene PROX1 is related to the Drosophila prospero gene, which is expressed in the developing central nervous system and lens-secreting cone cells. We found that the PROX1 gene had missense and nonsense mutations in 4 of 29 hematologic cell lines analyzed. Decreased mRNA expression was also observed in half of these cell lines by RT-PCR. The restoration of PROX1 gene expression after treatment with the demethylating agent 5-aza-2'-deoxycytidine, as well as bisulfite sequencing analysis, indicated that gene silencing is caused by DNA hypermethylation at intron 1. Such hypermethylation was also seen in primary lymphomas (56.3%, 18/32) in a tumor-specific manner. These findings indicate that the profile of the PROX1 gene corresponds to that of a candidate tumor-suppressor gene.

We recently identified HIV-2 CRF01_AB cases in Japan. This ectopic observation of the virus outside its original endemic area suggests an ongoing global spread of HIV-2 CRF01_AB.

We detected several types of human immunodeficiency virus type 1 (HIV‐1) variants with an insertion mutation in the p6gag and p6pol genes in eight of twenty‐two (36.4%) patients who possessed drug‐resistant viruses under highly active antiretroviral therapy (HAART). It was characteristic that a conserved proline‐rich motif “PTAPP” in the N‐terminus of p6gag protein was completely or partially duplicated in all cases. Five among the eight cases were retrospectively investigated in terms of the occurrence of dynamic change in the gag gene between the inserted and wild‐type HIV‐1 in the course of HAART. The longitudinal analysis revealed the following: 1) The inserted‐type viruses were selected over the wild‐type during HAART in three cases in which the both types coexisted in the beginning of the therapy. 2) In two cases in which the inserted‐type HIV‐1 alone was detected before the beginning of HAART, the inserted‐type HIV‐1 alone was continuously detected during the therapy. The inserted‐type HIV‐1 was also detected in four of thirty‐nine (10.3%) therapy‐naive patients. However, the frequency of inserted‐type HIV‐1 detection in the HAART‐receiving patients is significantly higher than that in the therapy‐naive patients (P=0.02). These results suggest that this type of insertion mutation is a polymorphism of the p6gag and p6pol genes, however, it consequently gave an advantage on proliferation and/or survival of the HIV‐1 variant under the presence of antiretroviral drugs.

ObjectiveThe human APOBEC3 family of proteins potently restricts HIV-1 replication APOBEC3B, one of the family genes, is frequently deleted in human populations. Two previous studies reached inconsistent conclusions regarding the effects of APOBEC3B loss on HIV-1 acquisition and pathogenesis. Therefore, it was necessary to verify the effects of APOBEC3B on HIV-1 infection in vivo.MethodsIntact (I) and deletion (D) polymorphisms of APOBEC3B were analyzed using PCR. The syphilis, HBV and HCV infection rates, as well as CD4+ T cell counts and viral loads were compared among three APOBEC3B genotype groups (I/I, D/I, and D/D). HIV-1 replication kinetics was assayed in vitro using primary cells derived from PBMCs.ResultsA total of 248 HIV-1-infected Japanese men who have sex with men (MSM) patients and 207 uninfected Japanese MSM were enrolled in this study. The genotype analysis revealed no significant differences between the APOBEC3B genotype ratios of the infected and the uninfected cohorts (p = 0.66). In addition, HIV-1 disease progression parameters were not associated with the APOBEC3B genotype. Furthermore, the PBMCs from D/D and I/I subjects exhibited comparable HIV-1 susceptibility.ConclusionOur analysis of a population-based matched cohort suggests that the antiviral mechanism of APOBEC3B plays only a negligible role in eliminating HIV-1 in vivo.