ABSTRACT
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.
Subject(s)
Cytomegalovirus Infections , Cytomegalovirus , Breast Feeding , Cytomegalovirus/genetics , Female , Humans , Incidence , Infant , Infant, Newborn , Infant, Premature , Milk, HumanSubject(s)
Genetic Variation , HIV Infections/virology , HIV Protease/genetics , Base Sequence , Drug Resistance, Viral , HIV-1/enzymology , Humans , Mexico , MutationABSTRACT
Protease is one of three enzymes encoded within HIV's pol gene, responsible for the cleavage of viral Gag-Pol polypeptide into mature viral proteins and a target of current anti-retroviral therapy. Protease diversity analysis in Latin America has been lacking in spite of extensive studies of protease-inhibitor resistance mutations. We studied the diversity of 777 Mexican protease sequences and found that all were subtype B except one (CRF02_AG). Phylogenetic analysis suggested the existence of six different clades with geospecific contributions. Thirty-three percent of sites were conserved, 25% had conservative substitutions, and 41% exhibited physicochemical changes. The most conserved regions surrounded the active site, most of the flap domain, and a region between the 60's loop and C-terminal triad. A single sequence exhibited an active site mutation (T26S). Variable sites were mapped to a crystallographic structure, providing further insight into the distribution and functional relevance of variable sites among Mexican isolates.
Subject(s)
Genetic Variation , HIV Infections/virology , HIV Protease/genetics , HIV-1/enzymology , HIV-1/genetics , Anti-Retroviral Agents/pharmacology , Drug Resistance, Viral/genetics , HIV Infections/epidemiology , HIV-1/drug effects , Humans , Mexico , Models, Molecular , Mutation, Missense , Phylogeny , Sequence Analysis, ProteinABSTRACT
Occipital condylar fractures (OCFs) causing delayed onset lower cranial nerve paralysis (LCNPs) are rare. We present a 7-year-old Friesian horse with delayed onset dysphagia caused by vagus nerve (CNX) paralysis and suspicion of glossopharyngeal nerve (CNIX) paralysis developed several days after a minor head injury. Endoscopic examination revealed right laryngeal hemiplegia and intermittent dorsal displacement of the soft palate. An area of submucosal hemorrhage and bulging was appreciated over the dorsal aspect of the medial compartment of the right guttural pouch. Radiological examination of the proximal cervical region showed rotation of the atlas and the presence of a large bone fragment dorsal to the guttural pouches. Occipital condyle fracture with delayed onset cranial nerve paralysis was diagnosed. Delayed onset cranial nerve paralysis causing dysphagia might be a distinguishable sign of OCF in horses. Delayed onset dysphagia after head injury should prompt equine clinicians to evaluate the condition of the atlanto-occipital articulation and skull base.
Subject(s)
Fractures, Bone/veterinary , Horse Diseases/etiology , Horses/injuries , Occipital Bone/injuries , Vagus Nerve Injuries/veterinary , Animals , Fractures, Bone/pathology , Horse Diseases/pathology , Male , Vagus Nerve/pathology , Vagus Nerve Injuries/pathologyABSTRACT
Polymorphisms located within the MHC have been linked to many disease outcomes by mechanisms not yet fully understood in most cases. Variants located within untranslated regions of HLA genes are involved in allele-specific expression and may therefore underlie some of these disease associations. We determined sequences extending nearly 2 kb upstream of the transcription start site for 68 alleles from 57 major lineages of classical HLA class I genes. The nucleotide diversity within this promoter segment roughly follows that seen within the coding regions, with HLA-B showing the highest (â¼1.9%), followed by HLA-A (â¼1.8%), and HLA-C showing the lowest diversity (â¼0.9%). Despite its greater diversity, HLA-B mRNA expression levels determined in 178 European Americans do not vary in an allele- or lineage-specific manner, unlike the differential expression levels of HLA-A or HLA-C reported previously. Close proximity of promoter sequences in phylogenetic trees is roughly reflected by similarity of expression pattern for most HLA-A and -C loci. Although promoter sequence divergence might impact promoter activity, we observed no clear link between the phylogenetic structures as represented by pairwise nucleotide differences in the promoter regions with estimated differences in mRNA expression levels for the classical class I loci. Further, no pair of class I loci showed coordinated expression levels, suggesting that distinct mechanisms across loci determine their expression level under nonstimulated conditions. These data serve as a foundation for more in-depth analysis of the functional consequences of promoter region variation within the classical HLA class I loci.
Subject(s)
HLA-A Antigens/genetics , HLA-B Antigens/genetics , HLA-C Antigens/genetics , Promoter Regions, Genetic/genetics , Alleles , Base Sequence , Cell Line , Genotype , Humans , Molecular Sequence Data , Phylogeny , Polymorphism, Genetic , Sequence Analysis, DNAABSTRACT
The viral infectivity factor (Vif) is an HIV accessory protein that counteracts host antiviral proteins of the APOBEC3 family. Accumulating evidence highlights the pivotal role that accessory HIV proteins have on disease pathogenesis, a fact that has made them targets of interest for novel therapeutic and preventive strategies. Little is known about Vif sequence diversity outside of African or white populations. Mexico is home to Americas' third largest HIV-affected population and Mexican Hispanics represent an ever-increasing U.S. minority. This study provides a detailed analysis of the diversity seen in 77 Mexican Vif protein sequences. Phylogenetic analysis shows that most sequences cluster with HIV-1 subtype B, while less than 10% exhibit greater similarity to subtype D and A subtypes. Although most functional motifs are conserved among the Mexican sequences, substantial diversity was seen in some APOBEC binding sites, the nuclear localization inhibitory signal, and the CBFß interaction sites.