The inhibitory receptor programmed death-1 (PD-1) is upregulated on exhausted CD8+ T cells in HIV-infected individuals. Quigley et al. analyzed the transcriptional profile induced by PD-1 ligation and report that a transcription factor, BATF, is upregulated by PD-1 signaling and has a key role in PD-1–mediated inhibition of T cell function. CD8+ T cells in chronic viral infections such as HIV develop functional defects including loss of interleukin-2 (IL-2) secretion and decreased proliferative potential that are collectively termed 'exhaustion'1. Exhausted T cells express increased amounts of multiple inhibitory receptors, such as programmed death-1 (PD-1)2,3, that contribute to impaired virus-specific T cell function. Although reversing PD-1 inhibition is therefore an attractive therapeutic strategy, the cellular mechanisms by which PD-1 ligation results in T cell inhibition are not fully understood. PD-1 is thought to limit T cell activation by attenuating T cell receptor (TCR) signaling4,5. It is not known whether PD-1 also acts by upregulating genes in exhausted T cells that impair their function. Here we analyzed gene expression profiles from HIV-specific CD8+ T cells in individuals with HIV and show that PD-1 coordinately upregulates a program of genes in exhausted CD8+ T cells from humans and mice. This program includes upregulation of basic leucine transcription factor, ATF-like (BATF), a transcription factor in the AP-1 family. Enforced expression of BATF was sufficient to impair T cell proliferation and cytokine secretion, whereas BATF knockdown reduced PD-1 inhibition. Silencing BATF in T cells from individuals with chronic viremia rescued HIV-specific T cell function. Thus, inhibitory receptors can cause T cell exhaustion by upregulating genes—such as BATF—that inhibit T cell function. Such genes may provide new therapeutic opportunities to improve T cell immunity to HIV.

Zika virus is a flavivirus closely related to dengue, West Nile, and yellow fever viruses. Although spread is primarily by Aedes species mosquitoes, two instances of sexual transmission of Zika virus have been reported, and replicative virus has been isolated from semen of one man with hematospermia. On February 5, 2016, CDC published recommendations for preventing sexual transmission of Zika virus. Updated prevention guidelines were published on February 23. During February 6-22, 2016, CDC received reports of 14 instances of suspected sexual transmission of Zika virus. Among these, two laboratory-confirmed cases and four probable cases of Zika virus disease have been identified among women whose only known risk factor was sexual contact with a symptomatic male partner with recent travel to an area with ongoing Zika virus transmission. Two instances have been excluded based on additional information, and six others are still under investigation. State, territorial, and local public health departments, clinicians, and the public should be aware of current recommendations for preventing sexual transmission of Zika virus, particularly to pregnant women. Men who reside in or have traveled to an area of ongoing Zika virus transmission and have a pregnant partner should abstain from sexual activity or consistently and correctly use condoms during sex with their pregnant partner for the duration of the pregnancy.

We report on 9 cases of male-to-female sexual transmission of Zika virus in the United States occurring January–April 2016. This report summarizes new information about both timing of exposure and symptoms of sexually transmitted Zika virus disease, and results of semen testing for Zika virus from 2 male travelers.

CDC issued interim guidance for the prevention of sexual transmission of Zika virus on February 5, 2016. The following recommendations apply to men who have traveled to or reside in areas with active Zika virus transmission and their female or male sex partners. These recommendations replace the previously issued recommendations and are updated to include time intervals after travel to areas with active Zika virus transmission or after Zika virus infection for taking precautions to reduce the risk for sexual transmission. This guidance defines potential sexual exposure to Zika virus as any person who has had sex (i.e., vaginal intercourse, anal intercourse, or fellatio) without a condom with a man who has traveled to or resides in an area with active Zika virus transmission. This guidance will be updated as more information becomes available.

Zika virus is an emerging mosquito-borne flavivirus. Recent outbreaks of Zika virus disease in the Pacific Islands and the Region of the Americas have identified new modes of transmission and clinical manifestations, including adverse pregnancy outcomes. However, data on the epidemiology and clinical findings of laboratory-confirmed Zika virus disease remain limited. During January 1, 2015-February 26, 2016, a total of 116 residents of 33 U.S. states and the District of Columbia had laboratory evidence of recent Zika virus infection based on testing performed at CDC. Cases include one congenital infection and 115 persons who reported recent travel to areas with active Zika virus transmission (n = 110) or sexual contact with such a traveler (n = 5). All 115 patients had clinical illness, with the most common signs and symptoms being rash (98%; n = 113), fever (82%; 94), and arthralgia (66%; 76). Health care providers should educate patients, particularly pregnant women, about the risks for, and measures to prevent, infection with Zika virus and other mosquito-borne viruses. Zika virus disease should be considered in patients with acute onset of fever, rash, arthralgia, or conjunctivitis, who traveled to areas with ongoing Zika virus transmission (http://www.cdc.gov/zika/geo/index.html) or who had unprotected sex with a person who traveled to one of those areas and developed compatible symptoms within 2 weeks of returning.