Highly attenuated smallpox vaccine protects rabbits and mice against pathogenic orthopoxvirus challenge.

The possible reemergence of smallpox through bioterrorism requires the preparation of adequate stockpiles of vaccine. Dryvax, the only US-licensed vaccinia virus smallpox vaccine, has an unacceptable safety profile in the pre-event setting. LC16m8 is a Japanese-licensed attenuated vaccinia virus strain that has been safely used in over 50,000 persons. Until now, efficacy of this vaccine was unproven. Using two animal models, we show that LC16m8 and Dryvax elicit comparable humoral immune responses after a single vaccination and equivalently protect against lethal poxvirus disease. Thus, LC16m8 shows promise as a safe and effective smallpox vaccine with the potential for replacing Dryvax.

Antimicrobial peptides from amphibian skin potently inhibit human immunodeficiency virus infection and transfer of virus from dendritic cells to T cells.

Topical antimicrobicides hold great promise in reducing human immunodeficiency virus (HIV) transmission. Amphibian skin provides a rich source of broad-spectrum antimicrobial peptides including some that have antiviral activity. We tested 14 peptides derived from diverse amphibian species for the capacity to inhibit HIV infection. Three peptides (caerin 1.1, caerin 1.9, and maculatin 1.1) completely inhibited HIV infection of T cells within minutes of exposure to virus at concentrations that were not toxic to target cells. These peptides also suppressed infection by murine leukemia virus but not by reovirus, a structurally unrelated nonenveloped virus. Preincubation with peptides prevented viral fusion to target cells and disrupted the HIV envelope. Remarkably, these amphibian peptides also were highly effective in inhibiting the transfer of HIV by dendritic cells (DCs) to T cells, even when DCs were transiently exposed to peptides 8 h after virus capture. These data suggest that amphibian-derived peptides can access DC-sequestered HIV and destroy the virus before it can be transferred to T cells. Thus, amphibian-derived antimicrobial peptides show promise as topical inhibitors of mucosal HIV transmission and provide novel tools to understand the complex biology of HIV capture by DCs.

Utilization of sialic acid as a coreceptor is required for reovirus-induced biliary disease.

Infection of neonatal mice with some reovirus strains produces a disease similar to infantile biliary atresia, but previous attempts to correlate reovirus infection with this disease have yielded conflicting results. We used isogenic reovirus strains T3SA- and T3SA+, which differ solely in the capacity to bind sialic acid as a coreceptor, to define the role of sialic acid in reovirus encephalitis and biliary tract infection in mice. Growth in the intestine was equivalent for both strains following peroral inoculation. However, T3SA+ spread more rapidly from the intestine to distant sites and replicated to higher titers in spleen, liver, and brain. Strikingly, mice infected with T3SA+ but not T3SA- developed steatorrhea and bilirubinemia. Liver tissue from mice infected with T3SA+ demonstrated intense inflammation focused at intrahepatic bile ducts, pathology analogous to that found in biliary atresia in humans, and high levels of T3SA+ antigen in bile duct epithelial cells. T3SA+ bound 100-fold more efficiently than T3SA- to human cholangiocarcinoma cells. These observations suggest that the carbohydrate-binding specificity of a virus can dramatically alter disease in the host and highlight the need for epidemiologic studies focusing on infection by sialic acid-binding reovirus strains as a possible contributor to the pathogenesis of neonatal biliary atresia.

Antiretroviral resistance testing for clinical management.

The advent of highly active antiretroviral therapy (HAART) has dramatically changed the management of HIV disease. These powerful regimens of drugs have reduced morbidity and mortality as well as number of hospitalizations among individuals with HIV. Nevertheless, many patients fail to achieve viral suppression. Various factors underlie this problem, but resistance to current medications has been increasingly recognized as an important element. Several methods of assessing antiretroviral resistance in HIV-1 are currently available. Phenotype assays directly assess the level of susceptibility of a virus to specific drugs. Genotype assays determine the presence of viral mutations that may affect viral susceptibility to a particular drug or class of drugs. An increasing amount of data indicates that antiretroviral resistance testing may improve response to therapy and increase the likelihood of achieving viral suppression. In this paper we review the available data regarding the role of antiretroviral resistance testing and compare the two different assays. We also discuss limitations of the current assays, interpretation of the data, and current consensus guidelines. Although many questions remain, antiretroviral resistance testing along with expert opinion can aid in the management of HIV disease.