phenylephrine-hydrochloride and Cytomegalovirus-Infections

Vaccination against the betaherpesvirus, human cytomegalovirus (HCMV) is a public health goal. However, HCMV has proved difficult to vaccinate against. Vaccination against single HCMV determinants has not worked, suggesting that immunity to a wider antigenic profile may be required. Live attenuated vaccines provide the best prospects for protection, but the question remains as to how to balance vaccine virulence with safety. Animal models of HCMV infection provide insights into identifying targets for virus attenuation and understanding how host immunity blocks natural, mucosal infection. Here, we evaluated the vaccine potential of a mouse cytomegalovirus (MCMV) vaccine deleted of a viral G protein-coupled receptor (GPCR), designated M33, that renders it attenuated for systemic spread. A single noninvasive olfactory ΔM33 MCMV vaccine replicated locally, but as a result of the loss of the M33 GPCR, it failed to spread systemically and was attenuated for latent infection. Vaccination did not prevent host entry of a superinfecting MCMV but spread from the mucosa was blocked. This approach to vaccine design may provide a viable alternative for a safe and effective betaherpesvirus vaccine.

Topics: Animals; Cytomegalovirus; Cytomegalovirus Infections; Cytomegalovirus Vaccines; Female; Immunity, Innate; Mice; Mice, Inbred BALB C; Muromegalovirus; Nose; Olfactory Mucosa; Proof of Concept Study; Superinfection; Vaccination; Vaccines, Attenuated

Topics: Child; Child Day Care Centers; Child, Preschool; Clothing; Cytomegalovirus; Cytomegalovirus Infections; Disease Transmission, Infectious; Humans; Infant; Nose

In healthy individuals, naturally acquired infections of human cytomegalovirus (HCMV) are generally asymptomatic. Animal models mimicking the natural primary HCMV infections in infants and adults are scarce. Here, neonatal and adult BALB/c mice were inoculated oronasally with a Belgian isolate HaNa1 of murine cytomegalovirus (MCMV). None of the mice showed clinical symptoms. In neonatal mice, a typical systemic infection occurred. In adult mice, viral replication was restricted to the nasal mucosa and submandibular glands. Infectious virus was not detected in trachea, oral mucosa, pharynx, esophagus, small intestines of both neonatal and adult mice at all time points. Nose was demonstrated to be the entry site. Double immunofluorescence staining showed that in nose infected cells were olfactory neurons and sustentacular cells in olfactory epithelium and were macrophages and dendritic cells in nasopharynx-associated lymphoid tissues (NALT). Neonatal and adult mice developed similar antibody response pattern, though former magnitude was lower. In summary, we have established intranasal (without anesthesia) infections of neonatal and adult mice with murine CMV HaNa1 strain, which mimic the range and extent of virus replication during natural primary HCMV infections in healthy infants and adults. These findings might bring new insights in the pathogenesis of natural primary CMV infections.

Topics: Animal Structures; Animals; Cytomegalovirus; Cytomegalovirus Infections; Disease Models, Animal; Female; Humans; Male; Mice; Mice, Inbred BALB C; Nose; Virulence; Virus Replication

Viruses transmit via the environmental and social interactions of their hosts. Herpesviruses have colonized mammals since their earliest origins, suggesting that they exploit ancient, common pathways. Cytomegaloviruses (CMVs) are assumed to enter new hosts orally, but no site has been identified. We show by live imaging that murine CMV (MCMV) infects nasally rather than orally, both after experimental virus uptake and during natural transmission. Replication-deficient virions revealed the primary target as olfactory neurons. Local, nasal replication by wild-type MCMV was not extensive, but there was rapid systemic spread, associated with macrophage infection. A long-term, transmissible infection was then maintained in the salivary glands. The viral m131/m129 chemokine homolog, which influences tropism, promoted salivary gland colonization after nasal entry but was not required for entry per se The capacity of MCMV to transmit via olfaction, together with previous demonstrations of experimental olfactory infection by murid herpesvirus 4 (MuHV-4) and herpes simplex virus 1 (HSV-1), suggest that this is a common, conserved route of mammalian herpesvirus entry.. Cytomegaloviruses (CMVs) infect most mammals. Human CMV (HCMV) harms people with poor immune function and can damage the unborn fetus. It infects approximately 1% of live births. We lack a good vaccine. One problem is that how CMVs first enter new hosts remains unclear. Oral entry is often assumed, but the evidence is indirect, and no infection site is known. The difficulty of analyzing HCMV makes related animal viruses an important source of insights. Murine CMV (MCMV) infected not orally but nasally. Specifically, it targeted olfactory neurons. Viral transmission was also a nasal infection. Like HCMV, MCMV infected cells by binding to heparan, and olfactory surfaces display heparan to incoming viruses, whereas most other mucosal surfaces do not. These data establish a new understanding of CMV infections and a basis for infection control.

Topics: Animals; Cytomegalovirus Infections; Humans; Mice; Muromegalovirus; Nose; Rodent Diseases; Salivary Glands; Smell; Virus Internalization

The immediate prosthetic rehabilitation of a patient with erosive cutaneous cytomegalovirus (CMV) is presented. Although CMV is a major cause of morbidity and mortality in immunocompromised patients, skin lesions are rarely discussed in the literature. Recognition of the susceptibility of medically compromised patients to infections that can cause extraoral and intraoral deformity is essential to prevention, early diagnosis, and prompt intervention of a life-threatening destructive debilitation. A method for rapidly fabricating a nasal prosthesis is described, and the importance of prompt esthetic and psychological rehabilitation is reviewed.

Topics: Adult; AIDS-Related Opportunistic Infections; Cytomegalovirus Infections; Female; Humans; Nose; Nose Deformities, Acquired; Prosthesis Design; Time Factors

Cebocephaly is a very rare congenital anomaly combining a severe midline facial malformation and holoprosencephaly. Here we report on first case of cebocephaly with semilobar holoprosencephaly, hypotelorism, and a single nostril due to intrauterine TORCH infection (Toxoplasmosis, other [syphilis, varicella-zoster, parvovirus B19], Rubella, Cytomegalovirus [CMV], and Herpes infections) in the English language literature. Chromosomal analysis showed normal karyotyping.

Topics: Abnormalities, Multiple; Adult; Craniofacial Abnormalities; Cytomegalovirus Infections; Fatal Outcome; Female; Herpes Simplex; Holoprosencephaly; Humans; Infant, Newborn; Karyotyping; Male; Microcephaly; Nose; Pregnancy; Pregnancy Complications, Infectious; Rubella; Tomography, X-Ray Computed

Although cytomegalovirus (CMV) infections are common throughout the world, little is known about the means of person-to-person transmission. To determine whether infection could be established by a respiratory route, studies were conducted in a murine CMV (MCMV) model by using intranasal inoculation. The infectious dose which resulted in pulmonary and systemic infection of half the mice was 100 plaque-forming units of MCMV. Here, infection was subclinical, but virus replicated in the lungs and subsequently disseminated via the blood to other organs within 7 days. The serum immunofluorescence antibody titer peaked by day 21. None of these mice died, although focal peribronchial interstitial pneumonitis was found in infected animals. In mice given greater than or equal to 10(4) plaque-forming units of MCMV intranasally, severe diffuse interstitial pneumonitis resulted uniformly, closely resembling that seen in immunocompromised patients and in newborn infants, and 20% of the animals died. Normal pulmonary architecture was obliterated by sheets of histiocytes, many containing MCMV intranuclear inclusions, and by accumulation of proteinaceous fluid in the interstitial and alveolar spaces. Of relevance to human disease, these experiments show that MCMV as a sole pathogen can cause severe interstitial pneumonitis in normal mice and that subclinical systemic infection results from respiratory inoculation of small amounts of virus.

Topics: Animals; Antibodies, Viral; Cytomegalovirus; Cytomegalovirus Infections; Female; Lung; Mice; Nose; Pneumonia, Viral

Topics: Complement Fixation Tests; Cross Infection; Cytomegalovirus; Cytomegalovirus Infections; Feces; Female; Hemagglutination Tests; Humans; Immunoglobulins; Infant, Newborn; Infant, Premature, Diseases; Male; Nose; Nurseries, Hospital; Pharynx; Transfusion Reaction; Urine

Topics: Cytomegalovirus Infections; Nose; Nose Diseases; Virus Diseases