HLA-G alleles and their impacts on placental HSV-1 infection in women from southern Brazil.

The Human Leukocyte Antigen G (HLA-G) is an immunoregulatory molecule with a critical role in pregnancy success. HLA-G alleles are associated with differential susceptibility to multiple conditions, including gestational problems, infectious diseases, and viral persistence. Of note, both herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) can impair HLA-G expression, interfering with HLA-G-associated immunoregulation. On the other hand, the impacts of HLA-G alleles on susceptibility to Herpesviridae infection is a neglected issue. Therefore, this study evaluated HLA-G allele frequencies and their associations with placental Herpesviridae infection in women from southern Brazil. Placenta samples were collected soon after delivery, and detection of viral DNA of HSV-1, HSV-2 and human cytomegalovirus (HCMV) was performed by polymerase chain reaction (PCR). A fragment of HLA-G (exons 2-4) was amplified by PCR, sequenced, and analyzed to allele determination. One hundred and seventy women had their alleles determined. Overall, 25 HLA-G alleles were found, distributed into 56 different genotypes. The most frequent alleles were G* 01:01:01 and G* 01:01:02, found in 37.9 % and 16.5 % of samples, respectively. Among the 170 women, 89 (52.4 %) tested positive for Herpesviridae DNA in the placenta, 55 (32.3 %) tested negative, 3 (1.8 %) were negative for HSV-1 and HSV-2 (with absent HCMV data), and 23 (13.5 %) were undetermined. The G* 01:01:01 allele was significantly associated with an increased risk of placental HSV-1 infection (p = 0.0151; OR=1.837; IC=1.108-3.045). This study describes new information concerning placental HLA-G alleles in women from southern Brazil and helps explain how genetic background can modify susceptibility to placental infections.

Impact of TLR7 and TLR9 polymorphisms on susceptibility to placental infections and pregnancy complications.

This study evaluated the impact of the TLR7 Gln11Leu (rs179008) and TLR9 -1237 T/C (rs5743836) single nucleotide polymorphisms (SNPs) on susceptibility to placental infections and pregnancy complications in 455 Brazilian women. Demographic, socioeconomic, gynecological, and clinical characteristics of the women were collected. Placental tissues were sampled from pregnant women and human and viral DNA was extracted. Human alphaherpesvirus 1 (Herpes simplex virus type 1, HSV-1), Human alphaherpesvirus 2 (Herpes simplex virus type 2, HSV-2) and Human betaherpesvirus 5 (Human cytomegalovirus, HCMV) were detected by nested PCR. TLR9 and TLR7 SNPs were genotyped by PCR amplification of bi-directional specific alleles (Bi-PASA) and restriction fragment length polymorphism (RFLP), respectively. Infections at the time of birth were detected in 45.71 % of women. The presence of the TT genotype (recessive model) of the TLR7 SNP was associated with increased susceptibility to HSV-1 infection (O.R. = 2.23, p = 0.05). The presence of the C allele of the TLR9 SNP, in heterozygosis or homozygosis (dominant model), decreased the infection risk by HCMV (O.R. = 0.31, p-mod<0.05). The TT genotype (recessive model) of the TLR7 SNP was significantly associated (p < 0.05) with increased occurrence of pre-treated hypertension. The codominant model of the TLR9 SNP was significantly associated (p < 0.05) with reduced risk of hospitalization during pregnancy. In combination, the AA/CT (TLR7-TLR9) genotypes significantly decreased the risk of placental infection by HSV-1 and/or HSV-2 (O.R. = 0.47, p = 0.02), the susceptibility to all infectious agents considered in combination (O.R. = 0.4, p = 0.00), and the need of hospitalization (O.R. = 0.48, p = 0.02). In conclusion, TLR7 and TLR9 SNPs are potential modulating factors for the risk of placental infections and pregnancy complications.

Co-infections associated with human immunodeficiency virus type 1 in pregnant women from southern Brazil: high rate of intraepithelial cervical lesions.

Human immunodeficiency virus type 1 (HIV-positive) pregnant women require specific prophylactic and therapeutic approaches. The efficacy of established approaches is further challenged by co-infection with other sexually transmitted diseases (STDs). The objective of this study was to determine the prevalence of co-infections in pregnant women infected with different HIV-1 subtypes and to relate these findings, together with additional demographic and clinical parameters, to maternal and infant outcomes. Blood samples from pregnant women were collected and tested for syphilis, hepatitis B virus (HBV) and hepatitis C virus (HCV). Human papillomavirus (HPV) diagnosis was evaluated by the presence of alterations in the cervical epithelium detected through a cytopathological exam. Medical charts provided patient data for the mothers and children. Statistical analyses were conducted with STATA 9.0. We found a prevalence of 10.8% for HCV, 2.3% for chronic HBV, 3.1% for syphilis and 40.8% for HPV. Of those co-infected with HPV, 52.9% presented high-grade intraepithelial lesions or in situ carcinoma. Prematurity, birth weight, Apgar 1' and 5' and Capurro scores were similar between co-infected and non-co-infected women. The presence of other STDs did not impact maternal and concept outcomes. More than half of the patients presenting cervical cytology abnormalities suggestive of HPV had high-grade squamous intraepithelial lesions or cervical cancer, evidencing an alarming rate of these lesions.

Co-infections associated with human immunodeficiency virus type 1 in pregnant women from southern Brazil: high rate of intraepithelial cervical lesions

Human immunodeficiency virus type 1 (HIV-positive) pregnant women require specific prophylactic and therapeutic approaches. The efficacy of established approaches is further challenged by co-infection with other sexually transmitted diseases (STDs). The objective of this study was to determine the prevalence of co-infections in pregnant women infected with different HIV-1 subtypes and to relate these findings, together with additional demographic and clinical parameters, to maternal and infant outcomes. Blood samples from pregnant women were collected and tested for syphilis, hepatitis B virus (HBV) and hepatitis C virus (HCV). Human papillomavirus (HPV) diagnosis was evaluated by the presence of alterations in the cervical epithelium detected through a cytopathological exam. Medical charts provided patient data for the mothers and children. Statistical analyses were conducted with STATA 9.0. We found a prevalence of 10.8 percent for HCV, 2.3 percent for chronic HBV, 3.1 percent for syphilis and 40.8 percent for HPV. Of those co-infected with HPV, 52.9 percent presented high-grade intraepithelial lesions or in situ carcinoma. Prematurity, birth weight, Apgar 1' and 5' and Capurro scores were similar between co-infected and non-co-infected women. The presence of other STDs did not impact maternal and concept outcomes. More than half of the patients presenting cervical cytology abnormalities suggestive of HPV had high-grade squamous intraepithelial lesions or cervical cancer, evidencing an alarming rate of these lesions.

Primary HIV-1 drug resistance in the C-terminal domains of viral reverse transcriptase among drug-naïve patients from Southern Brazil.

BACKGROUND: Major and accessory drug resistance mutations have been recently characterized in the C-terminal RT subdomains of HIV-1, connection and RNase H. However, their presence in treatment-naïve patients infected with HIV-1 non-B subtypes remains largely unknown. OBJECTIVES: To characterize the patterns of primary resistance at the C-terminal RT subdomains of HIV-1 infecting subjects in the southern region of Brazil, where HIV-1 subtypes B and C co-circulate. STUDY DESIGN: Plasma viral RNA was extracted from patients recently diagnosed for HIV infection (2005-2008). The protease and reverse transcriptase regions were PCR-amplified and sequenced. Infecting HIV subtypes were assigned by phylogenetic inference and drug resistance mutations were determined following the IAS consensus and recent reports on C-terminal RT mutations. RESULTS: The major mutation to NNRTI T369I/V was found in 1.8% of patients, while A376S was present in another 8.3%. In the RNase H domain, the compensatory mutation D488E was more frequently observed in subtype C than in subtype B (p=0.038), while the inverse was observed for mutation Q547K (p<0.001). The calculated codon genetic barrier showed that 22% of subtype B isolates, but no subtype C, carried T360, requiring two transitions to change into the resistance mutation 360V. CONCLUSIONS: Major resistance-conferring mutations to NNRTI were detected in 10% of RT connection domain viral sequences from treatment-naïve subjects. We showed for the first time that the presence of specific polymorphisms can constrain the acquisition of definite resistance mutations in the connection and RNase H subdomains of HIV-1 RT.