UL88 Mediates the Incorporation of a Subset of Proteins into the Virion Tegument.

Little is known about the human cytomegalovirus (HCMV) tegument protein UL88. Large-scale genomic studies have reported disparate results for UL88-null viruses, reporting both no phenotype and a >1-log decrease in virus titers. UL88 has also been reported to interact with UL69 and UL48, but the functional relevance of this interaction is unknown.

Inhibition of diverse opportunistic viruses by structurally optimized retrograde trafficking inhibitors.

Opportunistic viruses are a major problem for immunosuppressed individuals, particularly following organ or stem cell transplantation. Current treatments are non-existent or suffer from problems such as high toxicity or development of resistant strains. We previously published that a trafficking inhibitor that targets a host protein greatly reduces the replication of human cytomegalovirus.

Rerouting the traffic from a virus perspective.

Viruses are important human and animal pathogens causing disease that affect global health and the economy. One outcome of many virus infections is the regulation of cellular trafficking machinery. Viral proteins recruit and interact with cellular trafficking proteins to divert the normal trafficking of key proteins or to induce the formation of novel membrane structures in the host cell.

Potent Inhibition of Human Cytomegalovirus by Modulation of Cellular SNARE Syntaxin 5.

Unlabelled: Formation of the cytoplasmic viral assembly compartment (cVAC) is an important step for efficient human cytomegalovirus (HCMV) assembly. To do this, the virus must alter and repurpose the normal cellular balance of membrane and protein flux, a process that is not well understood. Although a recent screen identified three viral proteins essential for cVAC formation, less is known about the contribution of cellular factors.

Cleavage of the HPV16 Minor Capsid Protein L2 during Virion Morphogenesis Ablates the Requirement for Cellular Furin during De Novo Infection.

Infections by high-risk human papillomaviruses (HPV) are the causative agents for the development of cervical cancer. As with other non-enveloped viruses, HPVs are taken up by the cell through endocytosis following primary attachment to the host cell. Through studies using recombinant pseudovirus particles (PsV), many host cellular proteins have been implicated in the process.

Native human papillomavirus production, quantification, and infectivity analysis.

In a natural infection, human papillomavirus (HPV) replicates in a stratified and differentiated epithelium. We have developed an in vitro organotypic raft culture system that allows researchers to study HPV in its natural environment. Not only does this system reproduce the differentiation-dependent replication cycle of HPV, but it also allows for the production of high titers of native HPV virions.

Differential dependence on host cell glycosaminoglycans for infection of epithelial cells by high-risk HPV types.

Human papillomavirus (HPV) infection is the leading cause of cervical cancer world-wide. Here, we show that native HPV particles produced in a differentiated epithelium have developed different strategies to infect the host. Using biochemical inhibition assays and glycosaminoglycan (GAG)-negative cells, we show that of the four most common cancer-causing HPV types, HPV18, HPV31, and HPV45 are largely dependent on GAGs to initiate infection.

Differentiation-dependent interpentameric disulfide bond stabilizes native human papillomavirus type 16.

Genetic and biochemical analyses of human papillomavirus type 16 (HPV16) capsids have shown that certain conserved L1 cysteine residues are critical for capsid assembly, integrity, and maturation. Since previous studies utilized HPV capsids produced in monolayer culture-based protein expression systems, the ascribed roles for these cysteine residues were not placed in the temporal context of the natural host environment for HPV, stratifying and differentiating human tissue. Here we extend upon previous observation, that HPV16 capsids mature and become stabilized over time (10-day to 20-day) in a naturally occurring tissue-spanning redox gradient, by identifying temporal roles for individual L1 cysteine residues.

The E7 open reading frame acts in cis and in trans to mediate differentiation-dependent activities in the human papillomavirus type 16 life cycle.

Human papillomaviruses (HPVs) are the causative agents of several important genital and other mucosal cancers. The HPV16 E7 gene encodes a viral oncogene that is necessary for the continued growth of cancer cells, but its role in the normal, differentiation-dependent life cycle of the virus is not fully understood. The function of E7 in the viral life cycle was examined using a series of mutations of E7 created in the context of the complete HPV16 genome.

Cross-neutralization potential of native human papillomavirus N-terminal L2 epitopes.

Background: Human papillomavirus (HPV) capsids are composed of 72 pentamers of the major capsid protein L1, and an unknown number of L2 minor capsid proteins. An N-terminal "external loop" of L2 contains cross-neutralizing epitopes, and native HPV16 virions extracted from 20-day-old organotypic tissues are neutralized by anti-HPV16 L2 antibodies but virus from 10-day-old cultures are not, suggesting that L2 epitopes are more exposed in mature, 20-day virions. This current study was undertaken to determine whether cross-neutralization of other HPV types is similarly dependent on time of harvest and to screen for the most effective cross-neutralizing epitope in native virions.

Tissue-spanning redox gradient-dependent assembly of native human papillomavirus type 16 virions.

Papillomavirus capsids are composed of 72 pentamers reinforced through inter- and intrapentameric disulfide bonds. Recent research suggests that virus-like particles and pseudovirions (PsV) can undergo a redox-dependent conformational change involving disulfide interactions. We present here evidence that native virions exploit a tissue-spanning redox gradient that facilitates assembly events in the context of the complete papillomavirus life cycle.

An intervention to reduce residential insecticide exposure during pregnancy among an inner-city cohort.

Background: We previously reported widespread insecticide exposure during pregnancy among inner-city women from New York City. Here we report on a pilot intervention using integrated pest management (IPM) to reduce pest infestations and residential insecticide exposures among pregnant New York City African-American and Latina women (25 intervention and 27 control homes).

Methods: The IPM consisted of professional cleaning, sealing of pest entry points, application of low-toxicity pesticides, and education.

Biomarkers in maternal and newborn blood indicate heightened fetal susceptibility to procarcinogenic DNA damage.

Polycyclic aromatic hydrocarbons (PAHs) such as benzo[a]pyrene (BaP) are widespread air contaminants released by transportation vehicles, power generation, and other combustion sources. Experimental evidence indicates that the developing fetus is more susceptible than the adult to carcinogenic effects of PAHs, although laboratory studies in rodents suggest that the dose to fetal tissues is an order of magnitude lower than that to maternal tissues. To assess fetal versus adult susceptibility to PAHs and environmental tobacco smoke (ETS), we compared carcinogen-DNA adducts (a biomarker associated with increased cancer risk) and cotinine (a biomarker of tobacco smoke exposure) in paired blood samples collected from mothers and newborns in New York City.