A comparative analysis depicting the disease characteristics and phylogenetic signature of human cytomegalovirus infection in Human Immunodeficiency Virus 1 seropositive patients with end-organ retinitis and gastro-enteric diseases.

During advanced HIV infection, Human Cytomegalovirus (HCMV) has been proven to produce devitalizing end-organ diseases (EOD). The interactive co-existence of HIV and HCMV has been reported by many researchers and has been suggested to be linked with a more aggressive disease state. This study has been designed to bring forward an assessment of the clinical risk factors capable of defining the conditions of HCMV induced retinitis and gastro-enteric diseases among HIV1 seropositive patients. We also intended to analyse the phylogenetic variation if any, among the infecting virus types inducing the two separate clinical conditions. The patients were arranged in three different groups; (Group 1 with 26 individuals and group 2 and group 3 with 25 individuals each) based on their current status of HIV and HCMV infections. Serum ELISA, qualitative and quantitative detection of HCMV DNA, Real time mRNA expression study, sequencing, and phylogenetic analysis were performed. All statistical analyses and graphs were exercised using relevant software. We found that in HIV patients with HCMV induced end-organ diseases the components of the CXCL9, 10, 11-CXCR3 chemokine pathway is highly expressed with significant differences existing among patients with retinitis and gastrointestinal disease. We found that the gL gene sequences from the retinitis (HR) group clustered almost separately from that of the gastroenteritis (HG) group in the phylogenetic tree. It may be suggested that a form of natural selection pressure is working on the clinical HCMV strains creating a slight divergence in their phylogenetic lineage thereby helping them adapt to the particular tissue microenvironment they are colonizing.

An Intimate Alliance of DNA-Damage Response Network with Cell-Cycle Checkpoints Amid Events of Uncontrolled Cellular Proliferation: A Mini- Review.

There is close interdependence between cell survival, cell senescence, events of the cell cycle, apoptosis, malignancy development, and tumor responses to cancer treatment. Intensive studies and elaborate researches have been conducted on the functional aspects of oncogenes, tumor suppressor genes, apoptotic genes, and members guiding cell cycle regulation. These disquisitions have put forward the existence of a highly organized response pathway termed as a DNA-damage response network. The pathways detecting DNA damage and signaling are intensively linked to the events of cell-cycle arrest, cell proliferation, apoptosis, and cell senescence. DNA damage responses are complex systems that incorporate specific "sensor" and "transducer" proteins, for assessment of damage and signal transmission, respectively. These signals are thereafter relayed upon various "effector" proteins involved in different cellular pathways. It may include those governing cell-cycle checkpoints, participating in DNA repair, cell senescence, and apoptosis. This review discusses the role of the tumour suppressor gene, oncogenes, cell cycle checkpoint regulators during DNA damage response and regulation.

Insight into the distinctive paradigm of Human Cytomegalovirus associated intrahepatic and extrahepatic cholestasis in neonates.

Human Cytomegalovirus has been implicated as a probable cause for the development of hepatic cholestasis among neonates. Our study tried to ascertain the exact demographic, biochemical and immunological markers to differentially diagnose patients with HCMV associated intrahepatic and extrahepatic cholestasis and also decipher the phylogenetic variability among the viral strains infecting the two groups. A total of 110 neonates collected over a span of 2 years were selected for the study classified into four different groups based on the presence of hepatic cholestasis and active HCMV infection. Our analysis predicted that total Cholesterol, GGT, ALP and TNFα were the only significant biological markers with exact cut-off scores, capable of distinguishing between HCMV associated intrahepatic and extrahepatic cholestasis. We confirmed that in patients belonging to both of these groups, the inflammasome is activated and the extent of this activation is more or less same except for the initial activators NLRP3 and AIM2 respectively. When we performed two separate phylogenetic analyses with HCMV gM and gN gene sequences, we found that in both cases the sequences from the IHC and EHC groups formed almost separate phylogenetic clusters. Our study has shown that the HCMV clinical strains infecting at intrahepatic and extrahepatic sites are phylogenetically segregated as distinct clusters. These two separate groups show different physiological as well as immunological modulations while infecting a similar host.

A cross-sectional study exploring disease characteristics and phylogenetic nature of human cytomegalovirus among infected neonates with congenital nephrotic syndrome.

BACKGROUND: Congenital nephrotic syndrome (CNS) is a rare but serious condition which affects neonates and is caused by monogenic defects of glomerular structural proteins or congenital viral infections. Several reports have established a causal relationship between human cytomegalovirus (HCMV) intrauterine infection and CNS, but thorough study assessing parameters has not yet been done. METHODS: This study aimed to ascertain significant demographic, biochemical, serological, inflammatory and etiological parameters with 12 months follow-up to clinically identify and monitor neonates with HCMV-associated CNS and sought to decipher the phylogenetic nature of infecting strains. Differences between four patient groups (neonates < 4 weeks old) with or without CNS and HCMV infection were compared by unpaired t testing and one-way analysis of variance (ANOVA). Linear regression was performed to assess statistical significance among individual groups. Maximum-likelihood-based phylogenetic analysis was performed with HCMV gH gene sequences to compare clinically isolated and referenced NCBI strains. This was further supported by analysis of effective number of codons (ENc), codon adaptation index (CAI) and mRNA structural variation. RESULTS: Patients with HCMV-associated CNS were found to have significant variations in many studied parameters compared with controls. The majority of clinical strains formed a separate phylogenetic cluster defining them as somewhat distinct from standard reference strains, which was supported by the other analyses. CONCLUSION: This study defined parameters for monitoring cases of HCMV-associated CNS, which suggest the possible existence of a selection force acting and rendering these HCMV strains able to infect selective host tissues and cause specific disease types.