HCV genotypes are differently prone to the development of resistance to linear and macrocyclic protease inhibitors.

Background: Because of the extreme genetic variability of hepatitis C virus (HCV), we analyzed whether specific HCV-genotypes are differently prone to develop resistance to linear and macrocyclic protease-inhibitors (PIs).

Methods: The study includes 1568 NS3-protease sequences, isolated from PI-naive patients infected with HCV-genotypes 1a (N = 621), 1b (N = 474), 2 (N = 72), 3 (N = 268), 4 (N = 54) 5 (N = 6), and 6 (N = 73). Genetic-barrier was calculated as the sum of nucleotide-transitions (score = 1) and/or nucleotide-transversions (score = 2.

Selected amino acid changes in HIV-1 subtype-C gp41 are associated with specific gp120(V3) signatures in the regulation of co-receptor usage.

The majority of studies have characterized the tropism of HIV-1 subtype-B isolates, but little is known about the determinants of tropism in other subtypes. So, the goal of the present study was to genetically characterize the envelope of viral proteins in terms of co-receptor usage by analyzing 356 full-length env sequences derived from HIV-1 subtype-C infected individuals. The co-receptor usage of V3 sequences was inferred by using the Geno2Pheno and PSSM algorithms, and also analyzed to the "11/25 rule".

Comparative analysis of drug resistance among B and the most prevalent non-B HIV type 1 subtypes (C, F, and CRF02_AG) in Italy.

In recent years, increasing numbers of patients infected with HIV-1 non-B subtypes have been treated with modern antiretroviral regimens. Therefore, a better knowledge of HIV drug resistance in non-B strains is crucial. Thus, we compared the mutational pathways involved in drug resistance among the most common non-B subtypes in Italy (F, C, and CRF02_AG) and the B subtype.

Genetic and structural analysis of HIV-1 Rev responsive element related to V38A and T18A enfuvirtide resistance mutations.

Background: For the expression of late viral genes, HIV-1 efficiently exploits the nuclear export by using Rev viral protein, which specifically binds the RNA Rev Responsive Element (RRE). This region is contained within the gp120-gp41 encoding sequence. Enfuvirtide is the first approved HIV-1 fusion-inhibitor, and gp41 codons associated with primary enfuvirtide-resistance (amino-acids 36-45) are localized within the RRE structure.

Identification and structural characterization of novel genetic elements in the HIV-1 V3 loop regulating coreceptor usage.

Background: The interaction between HIV-1 gp120 and CCR5 N terminus is critical for R5-virus entry and affects CCR5 antagonists' activity. Knowledge of how different genetic signatures of gp120 V3 domain effect the strength of this interaction is limited.

Methods: HIV-1 coreceptor usage was assessed in 251 patients using enhanced-sensitivity Trofile assay and V3 sequencing plus tropism prediction by Geno2pheno algorithm.

Role of hepatitis B virus genetic barrier in drug-resistance and immune-escape development.

Background: Impact of hepatitis B virus genetic barrier, defined as the number and type of nucleotide substitutions required to overcome drug/immune selective pressure, on drug-resistance/immune-escape development is unknown.

Methods: Genetic barrier was calculated according to Van de Vijver (2006) in 3482 hepatitis B virus-reverse transcriptase/HBV surface antigen sequences from 555 drug-naïve patients and 2927 antiviral-treated patients infected with hepatitis B virus genotypes A-G.

Results: Despite high natural variability, genetic barrier for drug-resistance development is identical amongst hepatitis B virus genotypes, but varies according to drug-resistance mutation type.

Selected amino acid mutations in HIV-1 B subtype gp41 are associated with specific gp120v₃ signatures in the regulation of co-receptor usage.

Background: The third variable loop (V3) of the HIV-1 gp120 surface protein is a major determinant of cellular co-receptor binding. However, HIV-1 can also modulate its tropism through other regions in gp120, such as V1, V2 and C4 regions, as well as in the gp41 protein. Moreover, specific changes in gp41 are likely to be responsible for of damage in gp120-CCR5 interactions, resulting in potential resistance to CCR5 inhibitors.

Rapid prediction of sustained virological response in patients chronically infected with HCV by evaluation of RNA decay 48h after the start of treatment with pegylated interferon and ribavirin.

The combination of pegylated interferons (PEG-IFNs) and ribavirin represents the standard of care for the treatment of chronic HCV-infected patients, yet with a success rate around 50% in genotypes 1 and 4, high costs and side effects. Therefore, early prediction of sustained virological response (SVR) is a relevant issue for HCV-patients. We evaluated the association between SVR and decline of HCV-RNA at 48h in a prospective cohort of 145 HCV-patients treated with PEG-IFNs and ribavirin (males=69.