Population-based Influenza and Respiratory Syncytial Virus Hospitalizations and In-hospital Mortality Rates Among Mexican Children Less Than Five Years of Age.

BACKGROUND: Population-based information regarding the impact of respiratory syncytial virus (RSV) and influenza on hospital admissions and mortality is scant for many countries. METHODS: Prospective testing of RSV and influenza virus was undertaken in patients <5 years old admitted to hospital with acute respiratory infection (ARI) between July, 2014 and June, 2015, and mortality rates for children living in 3 municipalities in the state of San Luis Potosí were calculated. RESULTS: During the 12-month study period, 790 children living in these municipalities were admitted with ARI. RSV was detected in 245 (31%) and influenza in 47 (5.9%). History of preterm birth was recorded for 112 children on admission. For children <5 years old, ARI-, RSV- and influenza-associated admission rates were 23.2, 7.2 and 1.4 (per 1000 population), respectively. The corresponding admission rates per 1000 infants <1 year old were 78, 25.2 and 4.4. Preterm infant admission rates were 2 times higher than those of term infants. Six children died; RSV was detected in 4 (66.6%) of the deceased, while no deaths were associated with influenza. ARI and RSV in-hospital mortality rates for children <5 years were 0.18 and 0.12 per 1000 population. ARI and RSV mortality rates in preterm infants were 7 and 14 times higher than in term infants, respectively. CONCLUSIONS: RSV was associated with both high admission and in-hospital mortality rates in children <5 years old. Specific interventions, such as active or passive immunization, to prevent RSV infections are required to reduce ARI-associated infant mortality.

Ultrastructural and Functional Characterization of Mitochondrial Dynamics Induced by Human Respiratory Syncytial Virus Infection in HEp-2 Cells.

Human respiratory syncytial virus (hRSV) is the leading cause of acute lower respiratory tract infections in children under five years of age and older adults worldwide. During hRSV infection, host cells undergo changes in endomembrane organelles, including mitochondria. This organelle is responsible for energy production in the cell and plays an important role in the antiviral response. The present study focuses on characterizing the ultrastructural and functional changes during hRSV infection using thin-section transmission electron microscopy and RT-qPCR. Here we report that hRSV infection alters mitochondrial morphodynamics by regulating the expression of key genes in the antiviral response process, such as Mfn1, VDAC2, and PINK1. Our results suggest that hRSV alters mitochondrial morphology during infection, producing a mitochondrial phenotype with shortened cristae, swollen matrix, and damaged membrane. We also observed that hRSV infection modulates the expression of the aforementioned genes, possibly as an evasion mechanism in the face of cellular antiviral response. Taken together, these results advance our knowledge of the ultrastructural alterations associated with hRSV infection and might guide future therapeutic efforts to develop effective antiviral drugs for hRSV treatment.

Levels of Pathogenic Th17 and Th22 Cells in Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune condition characterized, among others, by tissue damage and activation/differentiation of proinflammatory lymphocytes. Accordingly, several studies have concluded that type 17 T helper (Th17) cells seem to have an important role in the pathogenesis of this condition. However, the strategy for the identification and analysis of proinflammatory Th17 cells in those studies has not been consistent and has usually been different from what was originally described. Therefore, we decided to evaluate the levels of Th17 cells in patients with RA employing an extended immune phenotype by using an eight-color multiparametric flow cytometry analysis. For this purpose, blood samples were obtained from 30 patients with RA and 16 healthy subjects, and the levels of Th17 and type 22 helper (Th22) lymphocytes were analyzed as well as the in vitro differentiation of peripheral blood mononuclear cells into Th17 lymphocytes induced by interleukin-23 (IL-23) and IL-1ß. We found significant enhanced levels of total Th17 lymphocytes (defined as CD4+IL-17+) as well as enhanced numbers of their pathogenic (defined as CD4+CXCR3+IL-17+IL-22+CD243+CD161+IFN-γ +IL-10-) and nonpathogenic (CD4+CXCR3+IL-17+IL-22-CD243-CD161-IFN-γ -IL-10+) cell subsets in patients with RA. Likewise, the number of Th22 (CD4+CXCR3+/-IL-17-IL-22+) was also increased in these patients compared to healthy controls. However, the in vitro induction/differentiation of pathogenic Th17 cells showed similar results in controls and patients with RA. Likewise, no significant associations were detected in patients with RA between the levels of Th17 or Th22 cells and clinical or laboratory parameters. Our data indicate that patients with RA show enhanced blood levels of the different subsets of Th17 cells and Th22 lymphocytes tested in this study and suggest that these levels are not apparently associated with clinical or laboratory parameters.

Incidence of congenital and postnatal cytomegalovirus infection during the first year of life in Mexican preterm infants.

Cytomegalovirus infection occurs commonly during infancy. Postnatal infection in term infants is usually asymptomatic; however, infection in preterm infants can be associated with clinical manifestations during the neonatal period. Nevertheless, few studies to assess the frequency of cytomegalovirus infection in preterm infants have been performed outside of high-income countries. We analyzed the incidence of congenital and postnatal cytomegalovirus infection in a cohort of preterm infants. Cytomegalovirus infection was detected during the neonatal period in four of 178 infants; in three of them, the virus was detected during the first 3 weeks of life and, therefore, congenital infection was confirmed (1.7% incidence). Postnatal infection was detected in 44 (36.4%) of 121 infants who were assessed after discharge from the neonatal intensive care unit. Cytomegalovirus infection was significantly associated with the duration of breastfeeding. In addition, we characterized cytomegalovirus strains detected in infants together with sequences available at GenBank, based on sequences of the UL18 gene. Cytomegalovirus UL18-sequences clustered in five distinct clades (A-E), and sequences obtained from infants in our study were distributed in four of the five clades; 44.4% of these sequences were included in clade E. Breastfeeding duration was shorter on average (5.6 months) in infants with sequences in clade E compared to infants with sequences in the other three clades (8.2 months; p = .07). In conclusion, we provide information regarding the high incidence of cytomegalovirus infection in preterm infants. Further studies are warranted to assess if cytomegalovirus strain characteristics are associated with the risk of infection acquisition during infancy.

Phylogenomics and population genomics of SARS-CoV-2 in Mexico during the pre-vaccination stage reveals variants of interest B.1.1.28.4 and B.1.1.222 or B.1.1.519 and the nucleocapsid mutation S194L associated with symptoms.

Understanding the evolution of the SARS-CoV-2 virus in various regions of the world during the Covid-19 pandemic is essential to help mitigate the effects of this devastating disease. We describe the phylogenomic and population genetic patterns of the virus in Mexico during the pre-vaccination stage, including asymptomatic carriers. A real-time quantitative PCR screening and phylogenomic reconstructions directed at sequence/structure analysis of the spike glycoprotein revealed mutation of concern E484K in genomes from central Mexico, in addition to the nationwide prevalence of the imported variant 20C/S:452R (B.1.427/9). Overall, the detected variants in Mexico show spike protein mutations in the N-terminal domain (i.e. R190M), in the receptor-binding motif (i.e. T478K, E484K), within the S1-S2 subdomains (i.e. P681R/H, T732A), and at the basis of the protein, V1176F, raising concerns about the lack of phenotypic and clinical data available for the variants of interest we postulate: 20B/478K.V1 (B.1.1.222 or B.1.1.519) and 20B/P.4 (B.1.1.28.4). Moreover, the population patterns of single nucleotide variants from symptomatic and asymptomatic carriers obtained with a self-sampling scheme confirmed the presence of several fixed variants, and differences in allelic frequencies among localities. We identified the mutation N:S194L of the nucleocapsid protein associated with symptomatic patients. Phylogenetically, this mutation is frequent in Mexican sub-clades. Our results highlight the dual and complementary role of spike and nucleocapsid proteins in adaptive evolution of SARS-CoV-2 to their hosts and provide a baseline for specific follow-up of mutations of concern during the vaccination stage.

Mitochondria and Mitochondrial DNA: Key Elements in the Pathogenesis and Exacerbation of the Inflammatory State Caused by COVID-19.

Background and Objectives. The importance of mitochondria in inflammatory pathologies, besides providing energy, is associated with the release of mitochondrial damage products, such as mitochondrial DNA (mt-DNA), which may perpetuate inflammation. In this review, we aimed to show the importance of mitochondria, as organelles that produce energy and intervene in multiple pathologies, focusing mainly in COVID-19 and using multiple molecular mechanisms that allow for the replication and maintenance of the viral genome, leading to the exacerbation and spread of the inflammatory response. The evidence suggests that mitochondria are implicated in the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which forms double-membrane vesicles and evades detection by the cell defense system. These mitochondrion-hijacking vesicles damage the integrity of the mitochondrion's membrane, releasing mt-DNA into circulation and triggering the activation of innate immunity, which may contribute to an exacerbation of the pro-inflammatory state. Conclusions. While mitochondrial dysfunction in COVID-19 continues to be studied, the use of mt-DNA as an indicator of prognosis and severity is a potential area yet to be explored.

Respiratory syncytial virus B sequence analysis reveals a novel early genotype.

Respiratory syncytial virus (RSV) is a major cause of respiratory infections and is classified in two main groups, RSV-A and RSV-B, with multiple genotypes within each of them. For RSV-B, more than 30 genotypes have been described, without consensus on their definition. The lack of genotype assignation criteria has a direct impact on viral evolution understanding, development of viral detection methods as well as vaccines design. Here we analyzed the totality of complete RSV-B G gene ectodomain sequences published in GenBank until September 2018 (n = 2190) including 478 complete genome sequences using maximum likelihood and Bayesian phylogenetic analyses, as well as intergenotypic and intragenotypic distance matrices, in order to generate a systematic genotype assignation. Individual RSV-B genes were also assessed using maximum likelihood phylogenetic analyses and multiple sequence alignments were used to identify molecular markers associated to specific genotypes. Analyses of the complete G gene ectodomain region, sequences clustering patterns, and the presence of molecular markers of each individual gene indicate that the 37 previously described genotypes can be classified into fifteen distinct genotypes: BA, BA-C, BA-CC, CB1-THB, GB1-GB4, GB6, JAB1-NZB2, SAB1, SAB2, SAB4, URU2 and a novel early circulating genotype characterized in the present study and designated GB0.

Peripheral Blood Mitochondrial DNA Levels Were Modulated by SARS-CoV-2 Infection Severity and Its Lessening Was Associated With Mortality Among Hospitalized Patients With COVID-19.

Introduction: During severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the virus hijacks the mitochondria causing damage of its membrane and release of mt-DNA into the circulation which can trigger innate immunity and generate an inflammatory state. In this study, we explored the importance of peripheral blood mt-DNA as an early predictor of evolution in patients with COVID-19 and to evaluate the association between the concentration of mt-DNA and the severity of the disease and the patient's outcome. Methods: A total 102 patients (51 COVID-19 cases and 51 controls) were included in the study. mt-DNA obtained from peripheral blood was quantified by qRT-PCR using the NADH mitochondrial gene. Results: There were differences in peripheral blood mt-DNA between patients with COVID-19 (4.25 ng/µl ± 0.30) and controls (3.3 ng/µl ± 0.16) (p = 0.007). Lower mt-DNA concentrations were observed in patients with severe COVID-19 when compared with mild (p= 0.005) and moderate (p= 0.011) cases of COVID-19. In comparison with patients with severe COVID-19 who survived (3.74 ± 0.26 ng/µl) decreased levels of mt-DNA in patients with severe COVID-19 who died (2.4 ± 0.65 ng/µl) were also observed (p = 0.037). Conclusion: High levels of mt-DNA were associated with COVID-19 and its decrease could be used as a potential biomarker to establish a prognosis of severity and mortality of patients with COVID-19.

Chemoresistance in Breast Cancer Patients Associated With Changes in P2X7 and A2A Purinergic Receptors in CD8+ T Lymphocytes.

Breast cancer (BRCA) is the most frequent cancer type that afflicts women. Unfortunately, despite all the current therapeutic strategies, many patients develop chemoresistance hampering the efficacy of treatment. Hence, an early indicator of therapy efficacy might aid in the search for better treatment and patient survival. Although emerging evidence indicates a key role of the purinergic receptors P2X7 and A2A in cancer, less is known about their involvement in BRCA chemoresistance. In this sense, as the chemotherapeutic treatment stimulates immune system response, we evaluated the expression and function of P2X7 and A2A receptors in CD8+ T cells before and four months after BRCA patients received neoadjuvant chemotherapy. The results showed an increase in the levels of expression of P2X7 and a decrease in the expression of A2A in CD8+ T cells in non-chemoresistant (N-CHR) patients, compared to chemoresistant (CHR) patients. Interestingly, in CHR patients, reduced expression of P2X7 occurs along with a decrease in the CD62L shedding and the production of IFN-γ. In the case of the A2A function, the inhibition of IFN-γ production was not observed after chemotherapy in CHR patients. A possible relationship between the modulation of the expression and function of the P2X7 and A2A receptors was found, according to the molecular subtypes, where the patients that were triple-negative and human epidermal growth factor receptor 2 (HER2)-enriched presented more alterations. Comorbidities such as overweight/obesity and type 2 diabetes mellitus (T2DM) participate in the abnormalities detected. Our results demonstrate the importance of purinergic signaling in CD8+ T cells during chemoresistance, and it could be considered to implement personalized therapeutic strategies.

Respiratory syncytial virus acute respiratory infection-associated hospitalizations in preterm Mexican infants: A cohort study.

BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of severe acute respiratory infections (ARI) in preterm infants. The incidence of RSV-associated hospitalizations has not been defined in Mexico. OBJECTIVES: To determine the incidence of ARI- and RSV-associated hospitalizations in preterm infants during the first year of life. METHODS: Prospective cohort study of 294 preterm infants followed up through monthly telephone calls and routine outpatient visits. Hospitalized children were identified through daily visits to pediatric wards of participating hospitals and through telephone calls. Respiratory samples were tested for RSV by RT-PCR. RESULTS: Mean gestational age of participating infants was 33 weeks. Ninety-six infants were diagnosed with bronchopulmonary dysplasia (BPD) and 17 with congenital heart disease (CHD); 11 had both conditions. There were 71 hospitalization episodes in 53 infants. Respiratory samples for RSV detection were available in 44 hospitalization episodes, and the result was positive in 16 (36.3%). At least one hospitalization for ARI was recorded in 33 of 96 participants with BPD, in seven of 17 with CHD, and 18 of 192 infants without these diagnoses. Five (71.4%) of CHD infants who required admission also had BPD. RSV-confirmed hospitalization rates were 9.4%, 5.9%, and 2.6% for infants with BPD, CHD, and otherwise healthy preterm infants, respectively. Attributable RSV admission frequencies were estimated to be 13.6%, 16.5%, and 4.1%, respectively. CONCLUSIONS: Mexican preterm infants, particularly those with BPD, have high rates of ARI- and RSVassociated hospitalizations. Specific interventions to reduce the incidence of severe infections in this highrisk group are required.

Respiratory syncytial virus A genotype classification based on systematic intergenotypic and intragenotypic sequence analysis.

Respiratory syncytial virus (RSV), a leading cause of lower respiratory tract infections, is classified in two major groups (A and B) with multiple genotypes within them. Continuous changes in spatiotemporal distribution of RSV genotypes have been recorded since the identification of this virus. However, there are no established criteria for genotype definition, which affects the understanding of viral evolution, immunity, and development of vaccines. We conducted a phylogenetic analysis of 4,353 RSV-A G gene ectodomain sequences, and used 1,103 complete genome sequences to analyze the totallity of RSV-A genes. Intra- and intergenotype p-distance analysis and identification of molecular markers associated to specific genotypes were performed. Our results indicate that previously reported genotypes can be classified into nine distinct genotypes: GA1-GA7, SAA1, and NA1. We propose the analysis of the G gene ectodomain with a wide set of reference sequences of all genotypes for an accurate genotype identification.

Severe Respiratory Syncytial Virus Infection in Hospitalized Children.

BACKGROUND: Lower respiratory tract infections (LRTI) are one of the most common causes of death worldwide. Respiratory syncytial virus (RSV) is a leading cause of LRTI in children. Despite of its epidemiological importance, there is limited information regarding the impact of this virus in Latin America. AIMS OF THE STUDY: We carried out a prospective study to establish the frequency and characteristics of RSV infections in hospitalized Mexican children. METHODS: 1,252 children hospitalized between November, 2012 and December, 2015 because of LRTI were included in the study. A respiratory sample was obtained for RSV detection by RT-PCR and information regarding clinical presentation, hospital course, and outcome was recorded. RESULTS: RSV was detected in 43.7% of children admitted with LRTI, in 43.3% of those admitted to the intensive care unit (ICU), and in 36.4% of those who died. Infants with RSV infection were younger, were diagnosed with bronchiolitis more frequently, and were less likely to have underlying disorders than those with RSV-negative LRTI. Among RSV-positive infants, admission to the ICU was associated with the presence of underlying conditions, pneumonia diagnosis, and young age. Four (0.73%) of the 547 infants with RSV infection died; death was more common in those with underlying disorders than previously healthy infants (3.8 vs. 0.2%, respectively; p = 0.02). CONCLUSION: RSV contributes to a large proportion of LRTI hospital admissions. Most children admitted with RSV infection do not have underlying conditions. However, severe infection requiring ICU admission and death are more common in those with underlying disorders.

Effect of cytomegalovirus infection and leukocyte immunoglobulin like receptor B1 polymorphisms on receptor expression in peripheral blood mononuclear cells.

Leukocyte immunoglobulin like receptor B1 (LILRB1) plays a significant role in a number of infectious, autoimmune, cardiovascular, and oncologic disorders. LILRB1 expression varies between individuals and may be associated with polymorphisms on the regulatory region of the LILRB1 gene, as well as to previous cytomegalovirus infection. In this study, the contribution of these two factors to LILRB1 expression in peripheral blood mononuclear cells of healthy young adults was analyzed. LILRB1 expression in NK cells, T cells, B cells and monocytes was significantly stronger in individuals who had had cytomegalovirus infection than in those who had not (P < 0.001, P < 0.001, P < 0.01, and P < 0.001, respectively). Overall, no differences in LILRB1 expression were observed between individuals with and without GAA haplotypes of the LILRB1 regulatory region. However, when analyzed according to cytomegalovirus infection status, significant differences in LILRB1+ NK cells were observed. A higher proportion of LILRB1+ cells was found in GAA+ than in GAA- individuals who had not been infected (P < 0.01), whereas GAA- individuals had a larger proportion of LILRB1+ cells than GAA+ individuals who were cytomegalovirus positive (P < 0.01). In conclusion, cytomegalovirus infection has a major effect on LILRB1 expression in NK and other mononuclear cells and polymorphisms in the LILRB1 regulatory region appear to have a modulatory influence over this effect.

Development of Novel Single-Chain Antibodies against the Hydrophobic HPV-16 E5 Protein.

The human papilloma virus type 16 infects genital mucosa with high prevalence in the oncogenesis of cervical and oropharyngeal cancers. The E5 protein of this virus is a small hydrophobic protein, whose expression generally decreases as the infection progresses to malignancy. These characteristics point to a role of E5 in the establishment of HPV infection and the initiation into cell transformation. The study of the HPV-16 E5 functions has been hindered because of the lack of antibodies. Detection is very difficult because of its hydrophobic nature, membrane location, and very low levels of expression. Thus, the objective of this study was to select single-chain antibodies against the full size E5 protein, which was coexpressed with maltose-binding protein. We report that the E5 protein was recognized by the antibody and was validated in W12 cells by fluorescent microscopy, including a colocalization with one of its host substrates. The use of this antibody could increase our knowledge about the functions of the oncogenic HPV-16 E5 protein during the earliest stages of keratinocyte infection in human.

Respiratory Syncytial Virus-A ON1 Genotype Emergence in Central Mexico in 2009 and Evidence of Multiple Duplication Events.

Background: Respiratory syncytial virus (RSV) is a leading cause of respiratory infections. An RSV-A genotype (ON1) that contains a 72-nt duplication was reported in 2012 and has since extended worldwide. Methods: We analyzed 345 respiratory samples obtained between 2003 and 2014 to assess the relevance of ON1 infections. Nucleotidic and deduced amino acid sequences from viruses detected in San Luis Potosí and sequences previously reported were analyzed. Results: RSV ON1 was detected in 105 samples. The earliest case of ON1 infection was detected in November 2009, almost 1 year prior to detection of this virus in Canada. Amino acid sequence analysis of the duplication region showed the presence of Y273N and L274P substitutions in RSV GA2 viruses that, when combined, resulted in 4 different GXXSPSQ sequence motifs at positions 272-278. Three of these motifs were present in both the original and duplicated regions of ON1 strains. Additional signature amino acid substitutions were observed in ON1 strains that have the different sequence motifs. Conclusions: ON1 strains include viruses that appear to be the result of at least 3 independent duplication events. Molecular data of strains from diverse geographical regions should help define the frequency and implications of this evolution mechanism.

Prevalence and 3-year persistence of human papillomavirus serotypes in asymptomatic patients in Northern Mexico.

OBJECTIVE: To investigate clinical outcomes and 3-year persistence of human papillomavirus (HPV) infections among women in Mexico. METHODS: A prospective study enrolled sexually active women attending primary healthcare clinics in metropolitan Monterrey, Mexico, between June 3 and August 30, 2002. Baseline data were collected and participants underwent HPV screening. Patients with HPV infections were asked to attend a repeat screening appointment after 3 years, when the same screening data were gathered. Descriptive analyses were performed and the prevalence of cervical lesions and viral infections were examined. RESULTS: In total, 1188 patients who underwent initial HPV screening were included. Cervical lesions were detected in 5 (0.4%) patients and 239 (20.1%) patients had HPV infections; 129 (54.0%) of these patients attended 3-year follow-up. Among the 357 HPV serotypes identified, the most prevalent serotypes were HPV-59, HPV-52, HPV-16, and HPV-56, detected 62 (17.4%), 38 (10.6%), 27 (7.6%), and 18 (5.0%) times, respectively. Of the 129 patients attending 3-year follow-up, 104 (80.6%) were clear from HPV infections, 13 (10.1%) patients had persistent HPV infections, and 12 (9.3%) had HPV infections with different HPV types. CONCLUSIONS: The HPV prevalence was 20.1% in the present study; the most prevalent infections were HPV-59, HPV-52, HPV-16, and HPV-56. At 3-year follow-up, 25 (19.4%) patients had HPV infections.

Intensive Care Unit Admission and Death Rates of Infants Admitted With Respiratory Syncytial Virus Lower Respiratory Tract Infection in Mexico.

BACKGROUND: Respiratory syncytial virus (RSV) is the most common etiology for acute respiratory infection hospital admissions in young children. Case fatality rates for hospitalized patients range between 0% and 3.4%. Recent reports indicate that deaths associated with RSV are uncommon in developed countries. However, the role of this virus as a current cause of mortality in other countries requires further examination. METHODS: Children with RSV infection admitted between May 2003 and December 2014 to a level 2 specialty hospital in Mexico were included in this analysis. Underlying risk factors, admission to the intensive care unit (ICU) and condition on discharge were assessed to determine the ICU admission and death rates associated to RSV infection. RESULTS: We analyzed data of 1153 patients with RSV infection in whom information regarding underlying illnesses and discharge status was available. Sixty patients (5.2 %) were admitted to the ICU and 12 (1.04 %) died. Relevant underlying conditions were present in 320 (27.7%) patients. Infants with underlying respiratory disorders (excluding asthma) and a history of prematurity had high ICU admission rates (17.1% and 13.8%, respectively). Mortality rates were highest for infants with respiratory disease (excluding asthma) (7.3%), cardiovascular diseases (5.9%) and neurologic disorders (5.3%). The ICU admission and death rates were higher in infants <6 months of age than in other age groups. CONCLUSIONS: The ICU admission rate and mortality rate in Mexican infants hospitalized with RSV infection were 5.2% and 1%, respectively. Mortality rates were high in infants with respiratory, cardiovascular and neurologic disorders.

Risk factors for severe influenza A-related pneumonia in adult cohort, Mexico, 2013-14.

During the 2013-14 influenza season, we assessed characteristics of 102 adults with suspected influenza pneumonia in a hospital in Mexico; most were unvaccinated. More comorbidities and severity of illness were found than for patients admitted during the 2009-10 influenza pandemic. Vaccination policies should focus on risk factors.

HLA-DRB1 Class II antigen level alleles are associated with persistent HPV infection in Mexican women; a pilot study.

BACKGROUND: Persistent infection with high-risk human papillomavirus (HPV) is a major risk factor for malignant lesions and cervical cancer. A widely studied element in the search for genetic factors influencing risk HPV infection diseases is allelic variation of the human leukocyte antigen (HLA) locus. The study was designed to search for HLA susceptibility alleles contributing to the persistence of HPV infection in Mexican women. METHODS: A total of 172 subjects were divided into three groups: 1) HPV-persistent patients; 2) HPV-cleared; and 3) HPV-reinfected patients. They were screened for HPV types using a polymerase chain reaction (PCR). PCR-sequence specific oligonucleotide probes (PCR-SSOP) was used for HLA DRB1 and DQB1 typing. RESULTS: We observed that HLA-DQB1*0501 allele might be associated with susceptibility of reinfection with HPV (p = 0.01, OR = 4.9, CI 95% = 1.3 -18.7). Allele frequency of HLA-DRB1*14 was particularly reduced in patients with cancer when compared with the HPV-persistent group (p = 0.04), suggesting that this allele is a possible protective factor for the development of cervical cancer (OR = 2.98). HLA-DRB1*07 might be associated with viral clearance (p = 0.04). CONCLUSIONS: Genetic markers for HPV infection susceptibility are different in each population, in Mexicans several HLA-DQB1 alleles might be associated with an enhanced risk for viral persistence. In contrast, DRB1*14, seems to confer protection against cervical cancer.